\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[greek,english]{babel}



\usepackage{float}








\begin{document}

\title{Interaction between long non-coding RNA and microRNA in lung diseases}



\author[1]{Jiaqi Li}%
\author[1]{Xiaoxiao Liu}%
\author[1]{Liangliang Shi}%
\author[1]{Guochang Chen}%
\author[1]{Shengyu Huang}%
\author[1]{Mingzhuo Liu}%
\author[1]{Guanghua Guo}%
\affil[1]{First Affiliated Hospital of Nanchang University}%


\vspace{-1em}



  
  \date{May 15, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Non-coding RNAs are a group of RNAs that cannot synthesize proteins, but
are critical in the regulation of gene expression. A growing number of
studies discovered that miRNAs and lncRNAs, as the two major members of
the ncRNA family, play vital roles in regulating the physiological and
pathological processes of lung diseases, such as pneumonia, COPD
(chronic obstructive pulmonary disease), lung cancer, and asthma. These
interactions are intricately linked to the the regulation of immune
response, cell proliferation and apoptosis, cell differentiation and
polarization, cytokine secretion, or acts as tumor suppressors or
promoters. Understanding the role of ncRNAs in lung diseases might
provide novel insights into disease mechanisms and potential therapeutic
targets. In this review, we will go over the fundamental characteristics
and functions of miRNAs and lncRNAs, their potential interaction
mechanisms, then summarize the newly explorations on the role of these
interactions between lncRNAs and miRNAs in various lung diseases.%
\end{abstract}%



\sloppy


\textbf{Interaction between long non-coding RNA and microRNA in lung
diseases}

Jiaqi Li\textsuperscript{1}, Xiaoxiao Liu\textsuperscript{1}, Liangliang
Shi\textsuperscript{1}, Guochang Chen\textsuperscript{1}, Shengyu
Huang\textsuperscript{1}, Mingzhuo Liu\textsuperscript{1*} and Guanghua
Guo\textsuperscript{1*}

\textsuperscript{1} Medical Center of Burn Plastic and Wound Repair, The
First Affiliated Hospital of Nanchang University, Nanchang 330006, China

* Corresponding author

E-mail: ndyfy00655@ncu.edu.cn (G.G.); ndyfy05397@ncu.edu.cn (M.L.)

\textbf{Abstract}

Non-coding RNAs are a group of RNAs that cannot synthesize proteins, but
are critical in the regulation of gene expression. A growing number of
studies discovered that miRNAs and lncRNAs, as the two major members of
the ncRNA family, play vital roles in regulating the physiological and
pathological processes of lung diseases, such as pneumonia, COPD
(chronic obstructive pulmonary disease), lung cancer, and asthma. These
interactions are intricately linked to the the regulation of immune
response, cell proliferation and apoptosis, cell differentiation and
polarization, cytokine secretion, or acts as tumor suppressors or
promoters. Understanding the role of ncRNAs in lung diseases might
provide novel insights into disease mechanisms and potential therapeutic
targets. In this review, we will go over the fundamental characteristics
and functions of miRNAs and lncRNAs, their potential interaction
mechanisms, then summarize the newly explorations on the role of these
interactions between lncRNAs and miRNAs in various lung diseases.

\textbf{Keywords}

lncRNA; miRNA; RNA interaction; lung diseases

\textbf{Introduction}

Since non-coding RNAs (ncRNAs) without the ability to encode proteins,
they were long ignored as ``noise'' for a long time. We have only
recently realized the critical function ncRNAs play in the gene
transcription and translation process. Only about 2\% of human genes
have protein-coding potential, the remaining 98\% known as non-coding
RNAs, mainly include mainly include ribosomal RNA (rRNA), transfer RNA
(tRNA), ribozymes, small nuclear RNA (snRNA), small nucleolar RNA
(snoRNA), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and
circular RNA (circRNAs) {[}1{]} .The newly technologies such as
high-throughput sequencing (HTS) made it possible to detect RNA's
structure and expression, biological functions, and interactions of
RNA-RNA, RNA-DNA, and RNA-protein with high sensitivity and accuracy. To
further comprehend their functions and molecular mechanisms, then
establish the relationship with diseases of multiple species{[}2{]}.

LncRNA and miRNA bind and interact with each other in variety ways,
influencing downstream gene expression. Increasing evidences shows that
RNA-RNA interactions, especially lncRNA-miRNA interactions, are crucial
for gene expression in physiological and pathological processes.
Furthermore, lncRNA and miRNA, which are expressed in all kinds of
diseases and are involved in gene regulation, cellular metabolic
process, may be ideal biomarkers or therapeutic targets in the diagnosis
and treatment of cancer{[}3{]}.

The regulation of immune response, cell proliferation and apoptosis,
cell differentiation and polarization, and cytokine secretion are all
influenced by lncRNA-miRNA interactions, which also play a significant
role in the developing, advancing, and complications of lung diseases.
In this review, we summarize several potential regulatory mechanisms of
lncRNA-miRNA interactions: 1) lncRNA represses miRNA expression; 2)
ceRNA mechanism; 3) miRNA negatively regulates lncRNA; 4) lncRNA and
miRNA mutually repress each other; 5) LncRNA co-expresses with miRNA as
a primary-miRNA. Based on these mechanisms, the latest studies are
reviewed to reveal how lncRNA-miRNA interactions in relation to the six
prevalent lung diseases: pneumonia, COPD, lung tumors, asthma, ARDS, and
pulmonary fibrosis.

\textbf{1. LncRNA-miRNA interactions}

\textbf{1.1 LncRNA}

LncRNAs, longer than 200 nt, stimulate or inhibit transcription at the
transcriptional level, influence mRNA splicing, editing, translation, or
stability at the post-transcriptional level, and performing epigenetic
regulation{[}2{]}. As reside in various cells and subcellular
localizations, different lncRNAs serve diverse activities at different
times. The following categories can be determined by where they are
located on coding genes: 1) Intergenic (has no overlap with
protein-coding genes); 2) Antisense (enriched around the promoter or
terminator ends of the sense transcript); 3) Intronic (located in the
area of gene coding sites); 4) Divergent lncRNA (abundanted in the
vicinity of transcription start sites); 5) Pseudogenes (genes that have
no potential of coding) {[}4{]}. Divergent lncRNAs, which are
head-to-head overlap with the coding genes, account for about 20\% of
all lncRNAs. Divergent lncRNAs are strongly tied to essential growth and
developmental regulatory genes. Their functions are associated with
those of their neighboring coding genes, which can regulate those genes
in cis and encourage the diversification of higher eukaryotic
phenotypes{[}5{]}. With a countless number of lncRNA, more are
continually being found and labeled, and many lncRNAs' roles have not
yet been thoroughly investigated.

\textbf{1.2 MicroRNA}

MicroRNAs are small endogenous non-coding RNAs that are 18 to 25
nucleotides in size, with high conservation and specificity{[}6{]}.
MiRNA are crucial regulators of gene expression as post-transcriptional
silencing by binding and inhibiting target genes' translation, widely
involved in growth development and pathological processes{[}7{]}.

Intergenic miRNAs be transcribed with their own promoter independently,
whereas intragenic miRNAs be transcribed together with the host gene.
Long chain primary transcripts (pri-miRNAs) be transcribed and then cuts
by Drosha protein complex and generates pre-miRNA, after transported to
cytoplasm from nucleus, pre-miRNA being cut and modified by Dicer
enzymes to form mature miRNAs{[}8{]}. By partially complementary binding
to the target gene's 3' non-coding region (3'UTR), miRISCs
(miRNA-induced silencing complexes) leading to transcriptional
repression of the target mRNA with no impact on mRNA stability.
Completely complementary binding directly cleaves target mRNA.
Besides,miRNA also could lead mRNA deadenylation, transcriptional
repression or cleavage may trigger the deadenylative processes of
mRNA{[}9{]}. It has been also reported that miRNAs binding to the 5'-UTR
of mRNA may activate translation{[}10{]}. MiRNAs suppression and
activation of target mMiRNA regulate nearly all biological functions,
including cell division, proliferation, differentiation, apoptosis, and
cell cycle{[}11{]}.

MiRNA involved in genes regulation networks, miR-21, miR-29 family,
miR-27(a/b), miR-34 in oral fluids were shown to be biomarkers in the
tooth movement, modulating the process of osteoblastogenesis,
osteoclastogenesis, and extra-cellular matrix conformation
post-transcriptionally, and regulating the Physiological processes of
orthodontic-related bone and tissue remodeling{[}12{]}. MiR-1 and
miR-133, act as co-transcriptional and co-regulatory factors{[}13{]},
that are highly expressed in injured myocardial tissue, encapsulated in
exosomes and released into circulation, mediating the mobilization of
bone marrow progenitor cells from bone marrow to the peripheral
circulation and participating in the repair of myocardial
ischemia{[}14{]}.

\textbf{1.3 The potential mechanisms of lncRNA-miRNA interaction}

\textbf{1.3.1 LncRNA represses miRNA expression}

LncRNA bind with miRNA and suppress its expression by common binding
sites, or lncRNA directly suppressing miRNA precursors or primary
miRNAs, thereby lowering transcription product creation. Lnc-PFAR stems
pre-miR-141 maturation by binding with pre-miR-141 in 72 Nucleotide
binding domain, thus reducing miR-141 expression{[}15{]}. Rather than
direct bind and interact with mature miRNA, lnc uc.173 combined with
pri-miR-195 in its central stem region, destabilizing and enhancing
degradation of pri-miR-195, thus inhibiting Dorsha-mediated pri-miRNA
processing to pre-miRNA, and deregulate the expression of
miR-195{[}16{]}. In addition, the binding of lncRNA to miRNA, or miRNA
binding sponge, exerts a role in inhibiting miRNA function, while
further affect the mRNA levels of miRNA downstream targets, and this
mechanism of interaction by competitively binding miRNA to mRNA is known
as the ceRNA mechanism.

\textbf{1.3.2 CeRNA}

Competitive endogenous RNA (ceRNA) reveals a novel role of RNA-RNA
interaction, which has been heavily studied in recent years. At the
post-transcriptional level, miRNA attaches to the miRNA response element
(MRE) at the 3'-UTR end of the target gene and suppresses translation.
While certain lncRNAs produce MREs as well as function as miRNA sponges,
competing to other targeted mRNAs. The ceRNA mechanism refers to the
competitive binding between lncRNAs and mRNAs{[}17{]}. Other RNAs, such
as mRNA, pseudogenes, and circRNA also can serve in this way as
ceRNA{[}18{]}.

LncRNA Sox2ot from exosomes derived from highly invasive tumor cells,
binding to miR-200 as ceRNA mechanism, upregulate Sox2, to induce
epithelial-mesenchymal transition (EMT) and stem cell like properties in
different tumor cells, plays important roles in pancreatic ductal
adenocarcinoma invasion and metastasis{[}19{]}. Lnc SNHG1 promote
neuroinflammation, and neuronal toxicity via different mechanisms,in
the process of Alzheimer's disease, it could act as ceRNA for miR-137,
targeting KREMEN1 in the human primary neuron (HPN) cells, reduce cell
viability, promote cell apoptosis, decrease mitochondrial membrane
potential and the protein levels of cytochrome C{[}20{]}.

Whereas, there are some reports claiming that ceRNA only performs a
slight role in miRNA regulation, single ceRNA is unlikely to have any
biologically significant effects on the activity of miRNAs, or the
expression of genes{[}11, 21{]}. Most of RBP and miRNAs regulate gene
expression post-transcriptional have thousands of binding sites, the
numbers of these binding sites are highly dynamic as transcription
renders, only strong binding sites are likely to be altered by this
crosstalk effect{[}22{]}.

\textbf{1.3.3} \textbf{LncRNA co-expresses with miRNA as a pri-miRNA}

Some miRNAs host genes can encode both lncRNA and miRNA, one of the
functions of this class of lncRNAs is to act as primary miRNA, termed
lnc-pri-miRNAs, able to produce miRNAs{[}23{]}. Among them, lnc
LOC646329 can act as both a pri-miRNA to produce miR-29a/b1, and a
transcriptional enhancer to activate neighboring oncogenes and promote
Glioblastoma cell proliferation{[}24{]}. The genomic organization of lnc
MIR100HG, is located on human chromosome 11 (hsa chr11),generate
miR-100 and miR-125b,which co-represses several Wnt/\selectlanguage{greek}β-\selectlanguage{english}catenin negative
regulators,to rescue cetuximab responsiveness of cetuximab-resistant
colorectal cancer and head and neck squamous cell cancer cell
lines{[}25{]}.

\textbf{1.3.4 MiRNA negatively regulates lncRNA}

TMPO antisense RNA 1 (TMPO-AS1) gene, located on chromosome 12, served
as the diagnostic and prognostic marker of lung adenocarcinoma (LUAD).
MiR-383-5p binding with lnc TMPO-AS1 and inhibits its expression,
significantly reducing tumorigenesis and progression of LUAD{[}26{]}.

MALAT1 is each individually suppressed by MiR-216a,miR-216b and
miR-217. Especially, miR-216a and MALAT1's association further induced
G2/M arrest and cell cycle inhibition, decreased cell viability and
apoptosis in pancreatic cancer cells{[}27{]}.

\textbf{1.3.5 LncRNA and miRNA mutually repress each other}

While lnc MIR31HG can act as a sponge to bind miR-193b, miR-193b can
also directly target two binding sites on lnc MIR31HG, negatively
regulates lnc MIR31HG levels, induces apoptosis and G1/S phase arrest,
and reduces the cell growth of pancreatic ductal adenocarcinoma. These
mutually inhibitory effects contribute to the growth of tumors{[}28{]}.
A negative feedback pathway is formed between lnc MALAT1 and
miR-200c-3p. On the one hand, miR-200c-3p can mediate the silencing of
MALAT1, which plays a significant role in the migration and invasion of
pancreatic ductal adenocarcinoma and can be used as a prognostic
indicator. On the one hand, the high expression of lnc MALAT1 in
pancreatic ductal adenocarcinoma inhibits the expression of
miR-200c-3p{[}29{]}.

See the details of the mechanism in Fig 1.

\textbf{2. Functions in several lung diseases}

\textbf{2.1 Pneumonia}

Pneumonia can be brought on by a wide range of microorganisms, including
bacteria, viruses, mycoplasma, and fungus. When microorganisms invade,
nonspecific immunity responds positively with the release of
inflammatory factors and other immunomodulators from macrophages, which
are the primary source of inflammatory factors. In the same time,
macrophages directly engulf and kill microorganisms. Following this,
neutrophils and other immune cells are recruited, then neutrophils
perform pathogen clearance by phagocytosis of lysosomes, formation of
neutrophil extracellular traps (NETs), and degranulation to release
myeloperoxidase (MPO), gelatines B (MMP9), while also producing
inflammatory factors and chemokines{[}30{]}.Surface active proteins
(SP-A, SP-D, etc.) synthesized by alveolar II epithelial cells directly
inhibit microbial activity. The pulmonary immune system maintains a
balance between the clearance of invading pathogens and the functional
and ecological integrity.

The most common pathogens of hospital-acquired pneumonia are
Enterobacteriaceae, Staphylococcus aureus, Pseudomonas aeruginosa and
Acinetobacter baumannii{[}31{]}. In some cases, there may be multiple
bacterial infections, concurrent bacterial pneumonia and influenza, or
secondary bacterial infections after an exacerbation of a viral
infection. The most common pathogen for secondary bacterial infections
is Staphylococcus aureus, followed by Streptococcus pneumonia,
Haemophilus influenza, and group A streptococcus{[}32{]}. About 25\% of
patients develop secondary bacterial infections after influenza A (H1N1)
infection{[}33{]}.

Influenza A virus infection stimulates IFN-\selectlanguage{greek}β \selectlanguage{english}transcription, which in
turn upregulates lnc-ISG20 expression. lnc-ISG20 acts as a ceRNA
competing with ISG20 to bind miR-326, reducing the inhibition of ISG20
translation and negatively regulating the replication of influenza
A{[}34{]}. There are also retroviruses known as Prototype foamy virus
(PFV) that cause no clinical symptoms after infection. Lnc-RP5 binding
to miR-129-5p and boost its expression as a result of the infection,
repressing Notch1 to increase the unique internal promoter of PFV, thus
active the expression of the viral transcriptional transactivator, be
critical to the replication, expression, and transportation of
virus{[}35{]}.

Both lnc-ANRIL and miR-125a are associated with the severity and
pro-infammatory factors level of sepsis, also are high value predictive
biomaker for short-term sepsis risk and 28-day mortality{[}36{]}.
Additionally, lnc-ANRIL/miR-125a axis shows more efficient in the
prediction of the sepsis risk, correlation with the organ damage and a
series of inflammatory factors of sepsis{[}37{]}. Overexpression of lnc
NKILA leads to the upregulation of miR-21, inhibition of JNK/NF-\selectlanguage{greek}κ\selectlanguage{english}B
pathway, and reduces immune response and lung fibroblast apoptosis and
cell viability in pediatric pneumonia{[}38{]}.

Since Decemeber 2019, the rapid spread of the novel severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) transmitted via
respiratory droplets has led to a worldwide pandemic of the coronavirus
disease 2019 (COVID-19){[}39{]}. Patients who are infected may show no
symptoms for a brief period of time, and rapidly developing a high fever
and severe respiratory symptoms (cough, shortness of breath, etc.),
along with other nonspecific symptoms including malaise, myalgia,
nausea, and vomiting{[}40{]}.

It has been found that miR-146a-5p, miR-21-5p and miR-142-3p are
relatively lowly expressed and miR-15b-5p is highly expressed in the
serum of COVID-19 patients. Metastasis-associated lung adenocarcinoma
transcript 1 (MALAT1) can bind to miR-146a-5p and miR-142-3p and shows a
negative correlation with both{[}41{]}. Furthermore, patients with lower
miR-146a-5p expression levels responded to Tocilizumab less well {[}40).
MALAT1 and Nuclear-enriched autosomal transcript 1 (NEAT1) expression
was elevated in SARS-CoV-2-infected bronchial epithelial cells{[}42{]}.

NEAT1 target miR-21 in allergic rhinitis to inhibit its
anti-inflammatory effects and exacerbate the extent of the allergic
inflammatory response{[}43{]}. Therefore, it is hypothesized that MALAT1
silencing miR-146a-5 and NEAT1 targeting miR-21 may serve as targets for
COVID-19 therapeutic targeting.

\textbf{2.2COPD}

Airflow limitation with persistent respiratory symptoms and lung chronic
inflammation are the main features of COPD, which is characterized by
typical, prolonged dyspnea, cough and sputum, mainly due to long-term
immune response brought on smoking, occupational exposure, etc.{[}44{]}.
Increasing studies have shown that lncRNAs and miRNAs may be closely
related to the occurrence and development of COPD, could be potential
biomarkers and therapeutics{[}45{]}. As a predictor of susceptibility,
NEAT1 is also associated with disease severity and inflammation level,
has increased expression in the peripheral blood of COPD patients, and
functions in this way by down-regulation the expression of
miR-193a{[}46{]}. As a therapeutic way, RNA drugs are highly specific
and safe, may be one of the ideal method of administration for
COPD{[}44{]}. miR-146 affects pulmonary bronchial epithelial cells to
have anti-inflammatory effects in a number of chronic lung disorders.
Since lnc-PVT1 affects miR-146, its expression level can be utilized to
distinguish acute exacerbation of COPD (AECOPD) patients and stable cope
patients. lnc-PVT1 expression also predicting COPD susceptibility and
AECOPD~risk,~and is positively correlated~with inflammation factors
and~disease~severity stages{[}47{]}.Through RNA sequencing and
Bioinformatics prediction, Qian et al. Created a miRNA-mRN-lncRNA
ternary interaction network in non-smoking COPD patients and projected
that miR-218-5p/miR15a-RORA-LOC101928100/LINC00861 and
miR-218-5p/miR15a-TGF3-RORA-AS1 interactions play a significant role in
the pathogenesis of non-smoking COPD patients{[}48{]}.

Inducing oxidative stress from cigarette smoking results in severe
cellular damage and an inflammatory response, which is a key pathogenic
aspect of COPD. When cigarette smoke is applied to cells in vitro, it
can cause cytotoxicity and an immunological response. Bronchial
epithelial cells treated with smoke extraction have higher levels of
lncRNA MEG3, which causes higher cell apoptosis and inflammation by
sponge binding to miR-181a-2-3p {[}49{]}. Since lnc RP11-86H7.1
interacted with miR-9-5p through a ceRNA mechanism, which would lower
miR-9-suppression 5p's of NFKB1 production in bronchial epithelial
cells, Zhao et al. hypothesized that such ternary network may boost
PM2.5 related COPD{[}50{]}.

\textbf{2.3 Lung cancer}

Lung cancer is the leading cause of cancer-related deaths, non-small
cell lung cancer (NSCLC) which has an aggressive clinical course, is the
most common type of lung cancer, adenocarcinoma is the most common
histologic subtype of NSCLC, and squamous cell is the second common
subtype {[}51, 52{]}.

MALAT1, H19, and MEG3 are highly expressed in lung cancer tissue and
have been shown to be involved in all stages of lung cancer formation.
They are also important markers for the diagnosis and prognosis of lung
cancer. LncRNAs are crucial roles and lncRNA-miRNA interactions are the
most prevalent synergistic effects in tumors {[}21{]}. MALAT1 is
regarded as a predictive marker for lung adenocarcinoma and was one of
the earliest genes related to lung cancer to be discovered. The majority
of MALAT1 is found in nuclear speckles, where it interacts with a
variety of transcription factors, chromatin modifiers, and RNA binding
proteins (RBPs)~to control both transcriptional and post-transcriptional
gene expression{[}53{]}. Malat1 is an essential lncRNA implicated in
tumor growth, invasion, and metastatic processes even though it is not
necessitated for normal tissue growth and development{[}54{]}. By
increasing MALAT1 stability and modifying it through m6A methylation,
METTL3 promotes MALAT1 spongy binding to miR-1914-3p, which in turn
promotes YAP expression and YAP-induced metastasis and invasion~in
NSCLC{[}55{]}.

HOTAIR is linked to the formation of several tumors, and one of the
mechanisms is that HOTAIR controls several downstream targets via
different signaling pathways, which are linked to tumor cell motility,
proliferation, angiogenesis, invasion, and drug resistance{[}56{]}.
MiR-613 is downregulated by HOTAIR, that is an extremely low expression
in NSCLC~tissues,~which facilitates NSCLC invasion and metastasis
{[}57{]} and mediates NSCLC genesis. In NSCLC cells, miR-221 reduces
HOTAIR expression and increases apoptosis{[}58{]}. By interacting with
miR-149-5p, HOTAIR drives the emergence of cisplatin resistance in NSCLC
{[}59{]}. HOTAIR also mediates miR-217/DACH1 signaling pathway
regulating proliferation, migration, and invasion of lung cancer
cells{[}60{]}.

Other lncRNA-miRNA interactions have also been demonstrated to
contribute to lung tumorigenesis. For instance, in a feedback loop
formed by lnc ZEB1-AS1 and miR-409-3p/ZEB1, miR-409-3p functions as a
regulatory bridge, is suppressed by lnc ZEB1-AS1 thereby upregulating
ZEB1, which then binds to the lnc ZEB1-AS1 promoter regions~to~promote
tumorigenesis{[}61{]}. Lnc GACAT1 expression is increased in NSCLC
tissues and cell lines, spongiosely binds miR-422a~and inactivates the
YY1 transcription factor (YY1), which may be associated with~poorer
clinical outcomes for patients{[}62{]}.

Other lncRNA-miRNA interactions mechanisms in lung cancer see in the
table 1.\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
\begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
LncRNA\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
MiRNA\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Mechanism\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Downstream targets\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Functions\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Cancer type\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Reference\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ATB\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-590-5p\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
lncRNA represses miRNA expression\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NF-90\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ATB upregulated in lung tissue and promote tumorigenesis and cell
proliferation, migration, and Invasion\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Lung Squamous Carcinoma Cell\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}63{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
CHRF\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-489\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
lncRNA represses miRNA expression\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Myd88\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
lncRNA CHRF modulate miR-489/Myd88 axis to inhibit cell proliferation,
Migration, Invasion, Apoptosis\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NSCLC\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}64{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
CCAT1\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-218\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
lncRNA represses miRNA expression\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
BMI-1\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
lncRNA CCAT1 downregulate miR-218 then inhibit BMI-1 to promotes
anti-apoptosis and cell proliferation\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NSCLC\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}65{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
DLEU2\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-30c-5p\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ceRNA\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
SOX9\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
lncRNA DLEU2 downregulate miR-30c-5p and promote SOX9, contribute to
tumorigenesis and metastasis, shorter overall survival\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NSCLC\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}66{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
MBNL1-AS1\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-301b-3p\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ceRNA\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
TGFBR2\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
lncRNA~MBNL1-AS1 positively regulated TGFBR2 by competitively binding to
miR-301b-3p, promote proliferation, migration, invasion, drug
resistance, and sphere formation of cancer stem cell\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NSCLC\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}67{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
LINC00240\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-7-5p\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ceRNA\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
EGFR\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
LncRNA LINC00240 suppresses invasion and migration by sponging miR-7-5p
and induced the overexpression of EGFR\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NSCLC\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}68{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
XIST\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-335\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ceRNA\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
SOD2\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
XIST facilitated NSCLC progression by miR-335/SOD2/ROS signal pathway
inhibited pyroptotic cell death\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NSCLC\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}69{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
LINC00662\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-320d\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ceRNA\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
E2F1\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
LINC00662 promotes cancer progress by miR-320d/E2F1 axis\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NSCLC\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}70{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
MEG3\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-7-5p\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ceRNA\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
BRCA1\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
MEG3 increases apoptosis of lung cancer cells~by~competitive binding
to~microRNA-7-5p reducing the BRCA1~expression.\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NSCLC\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}71{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
LINC01436\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-30a-3p\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ceRNA\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
EPAS1\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
LINC01436 promotes lung cancer cell growth, migration, and
invasion\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
~NSCLC\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}72{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
CASC2\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-21\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
lncRNA represses miRNA expression\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
p53\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
CASC2 suppresses cell proliferation and enhances apoptosis.\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
LUAD\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}73{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
H19\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-107\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ceRNA\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NF1\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
H19 increases the proliferative and migratory abilities of cancer
cells\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NSCLC\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}74{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
H19\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-196b\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ceRNA\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
LIN28B\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
H19 accelerates cell proliferation in lung cancer\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
lung cancer\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}75{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
LINC00857\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-1179\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ceRNA\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
SPAG5\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
LINC00857 promoted cell growth and glycolysis and repressed
apoptosis\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
LUAD\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}76{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NNT-AS1\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-129-5p\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ceRNA\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NNT-AS1 increases lung cancer cells proliferation and invasion
ability\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NSCLC\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}77{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
SNHG16\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-520\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ceRNA\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
VEGF\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
SNHG16 drives proliferation, migration, and invasion of lung cancer
cell\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NSCLC\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}78{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
UCA1\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-383\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ceRNA\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
VEGFA\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
UCA1 increases cell proliferation, migration and invasion\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
LUAD\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}79{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
PGM5P4-AS1\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-1275\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ceRNA\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
LZTS3\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
PGM5P4-AS1 inhibiteS lung cancer cell proliferation, migration, and
invasion activities\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
lung cancer\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}80{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1308\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-124\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ceRNA\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ADAM15\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
facilitates NSCLC cell proliferation and invasion\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NSCLC\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}81{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
DLGAP1-AS1\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-193a-5p\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ceRNA\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
DTL\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
exhibits oncogenic properties\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NSCLC\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}82{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
GAS5\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-21\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ceRNA\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
PTEN\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
increases the radiosensitivity and promotes the IR-induced cell
apoptosis\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NSCLC\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}83{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
PVT1-5\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-126\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ceRNA\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
SLC7A5\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
promotes cell proliferation\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
lung cancer\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}84{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
SNHG3\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-1343-3p\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ceRNA\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NFIX\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
promotes the development of non-small cell lung cancer\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NSCLC\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}85{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
SNHG4\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-let-7e\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ceRNA\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
KDM3A\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
promotes cell viability, colony formation, invasion, migration, and
cycle progression while reducing apoptosis\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NSCLC\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}86{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
SNHG1\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-145-5p\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ceRNA\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
MTDH\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
promotes non-small cell lung cancer progression\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NSCLC\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}87{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
LOC146880\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miR-539-5p\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
miRNA negatively regulates lncRNA\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ENO1\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
declines phosphorylation of an oncogene, ENO1, and then reduces cell
proliferation and tumor progression\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NSCLC\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
{[}88{]}\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 1. Other lncRNA-miRNA interaction mechanisms in lung
cancer}

Abbreviation: NSCLC, non-small cell lung cancer; LUAD, Lung
adenocarcinoma.

\textbf{2.4 Asthma}

Asthma is one of the most prevalent chronic inflammatory diseases,
typically characterized by airway hyperresponsiveness and airway
obstruction, and nonspecific airway symptoms caused by specific triggers
(such as allergens, environmental factors, infections, etc.). Airway
remodeling, including thickening of the airway wall and narrowing of the
airway, can occur in younger children as a result of epithelial injury,
cilia failure, cupular cell proliferation, fibroblasts, and growth of
airway smooth muscle cells{[}89{]}. For now, there are approximately 300
million asthma patients worldwide{[}90{]}. Over the last 40 years, there
has been a significant surge on the prevalence, morbidity and mortality
associated with asthma among children{[}91{]}.

Through its association with miR-124, lnc-NEAT1 triggers the release of
a number of inflammatory cytokines, and it is linked to a high risk of
severe asthma exacerbations {[}92{]}. Besides this, lnc PVT1 suppresses
the expression of miR-149, increases inflammation in small airway
epithelial cells, and impairs cellular defense barrier function{[}93{]}.
Asthma-related lung inflammation is mediated by CD4+ T cells, and asthma
development is facilitated by enhanced T cell differentiation of Th2
cells. Asthma-induced lung inflammation is amplified as lnc MALAT1
competitively binds miR-155 with CTLA-4 through a ceRNA mechanism. This
can boost CTLA-4 expression, which in turn causes up- and
down-regulation of the essential Th1/Th2 transcription regulators T-bet
and GATA3{[}94{]}.

Airway smooth muscle cells (ASM) are the primary effector cells in
asthma, and several studies have revealed that ASM cells proliferate in
asthma patients and promote a more contractile ASM phenotype in response
to inflammatory factor stimulation{[}95{]}. The upstream~lnc NEAT1~was
identified to modulate SLC26A2 expression by targeting miR-9-5p, enhance
ASM cell proliferation, migration,~contraction, and boost inflammation
in child asthma patients{[}96{]}.

Platelet-derived growth factor BB (PDGF-BB) stimulates Malat1 expression
in airway smooth muscle cells, Malat1 interacts with miR-150 by a ceRNA
mechanism, significantly enhances the essential translation initiation
factor, eIF4E, and Akt signaling, promotes airway smooth muscle cells
proliferation and migration, airway remodeling in asthma{[}97{]}.
Meanwhile, there are studies demonstrated that lnc GAS5 acts on
miR-10a/BDNF axis{[}98{]}, lnc PVT1 acts on miR-590-5p/FSTL1
axis{[}99{]}, lnc Malat1 acts on miR-150-eIF4E/AKT axis{[}100{]}
influencing ASM cell proliferation and migration in asthma.

\textbf{2.5 ARDS}

ARDS was known as~non-cardiogenic respiratory failure
with~severely~impaired pulmonary function, hypoxemia, and decreased
pulmonary compliance, with around 30 million patients every
year{[}101{]} and~mortality rate ranging from 34.9\% to 46.1\% depending
on the severity{[}102{]}. ARDS is caused by pulmonary infections
(bacterial, viral, etc.), other~significant infections~(skin,
genitourinary system, etc.), burns, particularly smoke inhalation, and
all kinds of~traumas{[}103{]}. There are no specialized treatment
options, and therapy is still reliant on lung-protective mechanical
ventilation.

When microorganisms, irritant mediators, and so on infiltrate the
alveolar barrier, macrophages polarize from resident alveolar
macrophages to the M1 phenotype at an early stage in response to
Toll-like receptors (TLR) induced by infection, releasing
pro-inflammatory factors such as IL-1, IL-6, and TNF-\selectlanguage{greek}α, \selectlanguage{english}which are the
first hurdle of lung~immune response{[}104{]}, while pro-inflammatory
Inflammation is exacerbated by further activation and release of
pro-inflammatory factors, chemokines, adhesion molecules, and so on. The
main~mechanism of ARDS~is assumed to be the acute, widespread lung
inflammation caused by this overwhelming immune response {[}105{]}.

A large number of miRNAs, such as miR-146, miR-155, miR-221, and
miR-222, have been noted to be stimulated upon TLR signaling activation,
and lncRNAs such as Mirt2, THRIL, MALAT1, and lincRNA-21 are also
altered upon TLR activation and negatively regulate TLR signaling as
well as suppress pro-inflammatory factor expression{[}106{]}. MALAT1 is
highly expressed in~inflammation-activated macrophages, interacts with
NF-\selectlanguage{greek}κ\selectlanguage{english}B, inhibits TLR signaling, and~lowers~TNF-\selectlanguage{greek}α, \selectlanguage{english}IL-6~and other
inflammatory factors~{[}107{]}. HOTAIR affects the miR-30a-5p/PDE7A axis
in LPS-induced ARDS, increases the release of inflammatory factors, and
exacerbates the pulmonary inflammatory response{[}108{]}.

\textbf{2.6 pulmonary fibrosis}

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive
interstitial lung disease mainly occurs in the~elderly. It has a poor
prognosis, a high mortality rate, and prone to acute exacerbation~to
respiratory failure{[}109{]}. Its etiology is still~unknown, however, is
frequently associated with~smoking, occupational exposure, air
pollution, and infection. Damage and repair of alveolar epithelial cells
owing to numerous causes, activation of fibroblasts, stimulation of
fibropathic proliferation, recruitment and proliferation of immune cells
such as alveolar macrophages and lymphocytes, and modulation of the
fibrotic response {[}110{]}, gradual destruction of the normal structure
of the lung, and progressive decompensation of lung function IPF can't
be reversed or stopped once it starts, although a number of medications
now used to treat it can only slow its advancement{[}111{]}.

The epithelial-mesenchymal transition (EMT) is critical in the
advancement of pulmonary fibrosis since epithelial cells able
to~de-differentiate then~differentiate into mesenchymal cells, which
continually produce and accumulate extracellular matrix, directly tied
to signaling pathways such as TGF-1, Smad, and ERK/MAP {[}112{]}.
Silicosis is caused by long-term silica inhalation and deposition in the
lungs, which leads to diffuse pulmonary fibrosis. Macrophages are
prompted to release TGF-1, which causes lnc ATB expression in epithelial
cells and binds to miR-200c to increase ZEB1 expression in
silica-induced silicosis pulmonary fibrosis {[}113{]}. In addition,
miR-29b-2-5p and miR-34c-3p are targets for sponging binding downstream
of lnc ATB, upregulating the expression of MEKK2 and NOTCH2, enabling
lnc ATB to contribute to the acceleration of the EMT process {[}114{]}.
Lung epithelial cells express more proliferation and~EMT-related genes
when lnc NEAT1 interacts with miR-29c {[}115{]}. lnc RFAL binds to
miR-18a and activates fibroblasts via CTGF to accelerate the process of
lung fibrosis {[}116{]}, lnc RFAL also suppresses miR-26a expression,
therefore inhibiting miR-26a's anti-fibrotic action. A mutually
inhibitory feedback loop established between miR-26a and Smad2,
leads~lnc PFRL to increase fibroblast proliferation and transform~into
myofibroblast {[}117{]}.

Liu et al. ~reported that in silica-induced lung fibrosis in mice
fibroblasts,~the~overexpression of lnc PCAT29 elevated
miR-221~expression, inhibited TGF-\selectlanguage{greek}β\selectlanguage{english}1~in lung fibroblasts, and slowed the
lung fibrosis process through the RASAL1/ERK1/2 signaling
pathway~{[}118{]}.Through the miR-326/SP1 axis, lnc SNHG1 enhances
fibroblast migration, invasion, and fibrogenic molecule production
{[}119{]}, whereas lnc SHNG6 promotes fibroblast activation and collagen
accumulation via the miR-26a-5p/TGF-1-smads axis, inducing lung fibrosis
in mice {[}120{]}.

\textbf{3.Discussion and Prospect}

Lung illnesses frequently do not occur in isolation; instead, they may
develop in combination with other systemic diseases, or numerous lung
diseases may occur simultaneously, or due to a causative factor causes
the disease to appear in diverse processes with varying clinical
symptoms and disease types. ~Microorganisms, for example, might cause
pneumonia at an early stage, but severe pneumonia may cause ARDS or even
a systemic inflammatory response syndrome, which could~lead to pulmonary
fibrosis in a long term, pulmonary fibrosis~increases the risk of lung
cancer by 7\% to 20\%{[}121{]}. This review addresses the results and
developments of lncRNA-miRNA interactions in the development,
prevention, and therapy of various common and thoroughly researched lung
diseases. Some star lncRNA molecules have been extensively studied in a
variety of diseases.~MALAT1 and NEAT1, which are involved in acute and
chronic inflammation of numerous causes of lung, as well as MALAT1 and
HOTAIR, which are expressed in several tumors including lung cancer.

We further noticed that research into the mechanism of lncRNA-miRNA
interactions in lung diseases is more focused on the ceRNA mechanism, in
which lncRNA sponges binding miRNAs, suppresses miRNA binding, and
silences downstream mRNA translation. Finding potential biomarkers for
disease diagnosis, degree, prognosis, or targets for therapy required an
understanding of the mechanism of lung disease formation and the role
played by ncRNAs in the mechanism of cure. All of that is accomplished
by constructing the lncRNA-miRNA action network. However, the
involvement of lncRNA-miRNA interactions in lung diseases is a
sophisticated network of inter-crosstalk among innumerable ncRNAs, the
roles and processes of which are yet unclear.

\textbf{Acknowledgments}

none.

\textbf{Funding}

This work was supported by grants 82160376 and 81960352 from the
National Natural Science Foundation, China; by grants 20192BAB215029
from the Youth Science Foundation, Jiangxi Province, China; and by
grants 1210013001, Gan Po Talent 555 Project Leading Talent Training
Program of Science and Technology Department, Jiangxi Province, China.

\textbf{Competing Interests}

The authors have no relevant financial or non-financial interests to
disclose.

\textbf{Author Contributions}

All authors contributed to the study conception and design. Material
preparation by Liangliang Shi and Guochang Chen, the table was edited by
Xiaoxiao Liu. The first draft of the manuscript was written by Jiaqi Li,
reviewed and edited by Shengyu Huang, Funding acquisition by Mingzhuo
Liu, Supervision by Guanghua Guo. All authors read and approved the
final manuscript.

\textbf{Ethics approval}

This is a review and no ethical approval is required.

\textbf{References}

1. Clark MB, Amaral PP, Schlesinger FJ, Dinger ME, Taft RJ, Rinn JL, et
al. The reality of pervasive transcription. PLoS Biol.
2011;9(7):e1000625; discussion e1102.

2. Qian X, Zhao J, Yeung PY, Zhang QC, Kwok CK. Revealing lncRNA
Structures and Interactions by Sequencing-Based Approaches. Trends
Biochem Sci. 2019;44(1):33-52.

3. Peng Q, Wang J. Non-coding RNAs in melanoma: Biological functions and
potential clinical applications. Mol Ther Oncolytics. 2021;22:219-31.

4. Kung JT, Colognori D, Lee JT. Long noncoding RNAs: past, present, and
future. Genetics. 2013;193(3):651-69.

5. Luo S, Lu JY, Liu L, Yin Y, Chen C, Han X, et al. Divergent lncRNAs
Regulate Gene Expression and Lineage Differentiation in Pluripotent
Cells. Cell Stem Cell. 2016;18(5):637-52.

6. Zhang X, Yang F, Liu F, Tian Q, Hu M, Li P, et al. Conservation of
Differential Animal MicroRNA Processing by Drosha and Dicer. Front Mol
Biosci. 2021;8:730006.

7. Duchaine TF, Fabian MR. Mechanistic Insights into MicroRNA-Mediated
Gene Silencing. Cold Spring Harb Perspect Biol. 2019;11(3).

8. Gulyaeva LF, Kushlinskiy NE. Regulatory mechanisms of microRNA
expression. J Transl Med. 2016;14(1):143.

9. Fabian MR, Sonenberg N, Filipowicz W. Regulation of mRNA Translation
and Stability by microRNAs. In: Kornberg RD, Raetz CRH, Rothman JE,
Thorner JW, editors. Annual Review of Biochemistry, Vol 79. Annual
Review of Biochemistry. 792010. p. 351-79.

10. Ryczek N, Lys A, Makalowska I. The Functional Meaning of 5 \&
PRIME;UTR in Protein-Coding Genes. Int J Mol Sci. 2023;24(3).

11. Gebert LFR, MacRae IJ. Regulation of microRNA function in~animals.
Nat Rev Mol Cell Biol. 2019;20(1):21-37.

12. Kapoor P, Chowdhry A, Bagga DK, Bhargava D, Aishwarya S. MicroRNAs
in oral fluids (saliva and gingival crevicular fluid) as biomarkers in
orthodontics: systematic review and integrated bioinformatic analysis.
Prog Orthod. 2021;22(1):31.

13. Song Z, Gao R, Yan B. Potential roles of microRNA-1 and microRNA-133
in cardiovascular disease. RCM. 2020;21(1):57-64.

14. Cheng M, Yang J, Zhao X, Zhang E, Zeng Q, Yu Y, et al. Circulating
myocardial microRNAs from infarcted hearts are carried in exosomes and
mobilise bone marrow progenitor cells. Nat Commun. 2019;10(1):959.

15. Zhang T, Zhang G, Yang W, Chen H, Hu J, Zhao Z, et al. Lnc-PFAR
facilitates autophagy and exacerbates pancreatic fibrosis by reducing
pre-miR-141 maturation in chronic pancreatitis. Cell Death Dis.
2021;12(11):996.

16. Xiao L, Wu J, Wang JY, Chung HK, Kalakonda S, Rao JN, et al. Long
Noncoding RNA uc.173 Promotes Renewal of the Intestinal Mucosa by
Inducing Degradation of MicroRNA 195. Gastroenterology.
2018;154(3):599-611.

17. Yang C, Wu D, Gao L, Liu X, Jin Y, Wang D, et al. Competing
endogenous RNA networks in human cancer: hypothesis, validation, and
perspectives. Oncotarget. 2016;7(12):13479-90.

18. Moradi MT, Fallahi H, Rahimi Z. Interaction of long noncoding RNA
MEG3 with miRNAs: A reciprocal regulation. Journal of Cellular
Biochemistry. 2019;120(3):3339-52.

19. Li ZH, Jiang P, Li J, Peng MJ, Zhao X, Zhang X, et al. Tumor-derived
exosomal lnc-Sox2ot promotes EMT and stemness by acting as a ceRNA in
pancreatic ductal adenocarcinoma. Oncogene. 2018;37(28):3822-38.

20. Wang H, Lu B, Chen J. Knockdown of lncRNA SNHG1 attenuated
A\selectlanguage{greek}β\selectlanguage{english}25-35-inudced neuronal injury via regulating KREMEN1 by acting as a
ceRNA of miR-137 in neuronal cells. Biochemical and Biophysical Research
Communications. 2019;518(3):438-44.

21. Heydarzadeh S, Ranjbar M, Karimi F, Seif F, Alivand MR. Overview of
host miRNA properties and their association with epigenetics, long
non-coding RNAs, and Xeno-infectious factors. Cell Biosci.
2021;11(1):43.

22. Jens M, Rajewsky N. Competition between target sites of regulators
shapes post-transcriptional gene regulation. Nat Rev Genet.
2015;16(2):113-26.

23. Sun Q, Song YJ, Prasanth KV. One locus with two roles:
microRNA-independent functions of microRNA-host-gene locus-encoded long
noncoding RNAs. Wiley Interdiscip Rev RNA. 2021;12(3):e1625.

24. He D, Wu D, Muller S, Wang L, Saha P, Ahanger SH, et al.
miRNA-independent function of long noncoding pri-miRNA loci. Proc Natl
Acad Sci U S A. 2021;118(13).

25. Lu Y, Zhao X, Liu Q, Li C, Graves-Deal R, Cao Z, et al. lncRNA
MIR100HG-derived miR-100 and miR-125b mediate cetuximab resistance via
Wnt/\selectlanguage{greek}β-\selectlanguage{english}catenin signaling. Nat Med. 2017;23(11):1331-41.

26. Mu X, Wu H, Liu J, Hu X, Wu H, Chen L, et al. Long noncoding RNA
TMPO-AS1 promotes lung adenocarcinoma progression and is negatively
regulated by miR-383-5p. Biomedicine \& Pharmacotherapy.
2020;125:109989.

27. Zhang Y, Tang X, Shi M, Wen C, Shen B. MiR-216a decreases MALAT1
expression, induces G2/M arrest and apoptosis in pancreatic cancer
cells. Biochemical and Biophysical Research Communications.
2017;483(2):816-22.

28. Yang H, Liu P, Zhang J, Peng X, Lu Z, Yu S, et al. Long noncoding
RNA MIR31HG exhibits oncogenic property in pancreatic ductal
adenocarcinoma and is negatively regulated by miR-193b. Oncogene.
2016;35(28):3647-57.

29. Zhuo M, Yuan C, Han T, Cui J, Jiao F, Wang L. A novel feedback loop
between high MALAT-1 and low miR-200c-3p promotes cell migration and
invasion in pancreatic ductal adenocarcinoma and is predictive of poor
prognosis. BMC Cancer. 2018;18(1):1032.

30. Quinton LJ, Walkey AJ, Mizgerd JP. Integrative Physiology of
Pneumonia. Physiol Rev. 2018;98(3):1417-64.

31. Leone M, Bouadma L, Bouhemad B, Brissaud O, Dauger S, Gibot S, et
al. Hospital-acquired pneumonia in ICU. Anaesthesia Critical Care \&
Pain Medicine. 2018;37(1):83-98.

32. Metlay JP, Waterer GW, Long AC, Anzueto A, Brozek J, Crothers K, et
al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia.
An Official Clinical Practice Guideline of the American Thoracic Society
and Infectious Diseases Society of America. Am J Respir Crit Care Med.
2019;200(7):e45-e67.

33. MacIntyre CR, Chughtai AA, Barnes M, Ridda I, Seale H, Toms R, et
al. The role of pneumonia and secondary bacterial infection in fatal and
serious outcomes of pandemic influenza a(H1N1)pdm09. BMC Infect Dis.
2018;18(1):637.

34. Chai W, Li J, Shangguan Q, Liu Q, Li X, Qi D, et al. Lnc-ISG20
Inhibits Influenza A Virus Replication by Enhancing ISG20 Expression. J
Virol. 2018;92(16).

35. Xu S, Chen L, Tang Y, Yuan P, Yan J, Zheng Y, et al. Lnc-RP5
Regulates the miR-129-5p/Notch1/PFV Internal Promoter Axis to Promote
the Expression of the Prototype Foamy Virus Transactivator Tas. Virol
Sin. 2020;35(1):73-82.

36. Gui F, Peng H, Liu Y. Elevated circulating lnc-ANRIL/miR-125a axis
level predicts higher risk, more severe disease condition, and worse
prognosis of sepsis. J Clin Lab Anal. 2019;33(6):e22917.

37. Liu W, Geng F, Yu L. Long non-coding RNA MALAT1/microRNA 125a axis
presents excellent value in discriminating sepsis patients and exhibits
positive association with general disease severity, organ injury,
inflammation level, and mortality in sepsis patients. J Clin Lab Anal.
2020;34(6):e23222.

38. Wang D, Zhang J, Sun Y, Lv N, Sun J. Long non-coding RNA NKILA
weakens TNF-\selectlanguage{greek}α-\selectlanguage{english}induced inflammation of MRC-5 cells by miR-21
up-regulation. Artificial Cells, Nanomedicine, and Biotechnology.
2020;48(1):498-505.

39. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical
Characteristics of Coronavirus Disease 2019 in China. N Engl J Med.
2020;382(18):1708-20.

40. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC.
Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus
Disease 2019 (COVID-19): A Review. JAMA. 2020;324(8):782-93.

41. Tang H, Gao Y, Li Z, Miao Y, Huang Z, Liu X, et al. The noncoding
and coding transcriptional landscape of the peripheral immune response
in patients with COVID-19. Clin Transl Med. 2020;10(6):e200.

42. Vishnubalaji R, Shaath H, Alajez NM. Protein Coding and Long
Noncoding RNA (lncRNA) Transcriptional Landscape in SARS-CoV-2 Infected
Bronchial Epithelial Cells Highlight a Role for Interferon and
Inflammatory Response. Genes (Basel). 2020;11(7).

43. Wang R, Xue S, Liu Y, Peng M, Guo B. The correlation of long
non-coding RNA NEAT1 and its targets microRNA (miR)-21, miR-124, and
miR-125a with disease risk, severity, and inflammation of allergic
rhinitis. Medicine (Baltimore). 2021;100(4):e22946.

44. Alfahad AJ, Alzaydi MM, Aldossary AM, Alshehri AA, Almughem FA,
Zaidan NM, et al. Current views in chronic obstructive pulmonary disease
pathogenesis and management. Saudi Pharm J. 2021;29(12):1361-73.

45. Mei D, Tan WSD, Tay Y, Mukhopadhyay A, Wong WSF. Therapeutic RNA
Strategies for Chronic Obstructive Pulmonary Disease. Trends Pharmacol
Sci. 2020;41(7):475-86.

46. Ming X, Duan W, Yi W. Long non-coding RNA NEAT1 predicts elevated
chronic obstructive pulmonary disease (COPD) susceptibility and acute
exacerbation risk, and correlates with higher disease severity,
inflammation, and lower miR-193a in COPD patients. Int J Clin Exp
Pathol. 2019;12(8):2837-48.

47. Wang Y, Lyu X, Wu X, Yu L, Hu K. Long non-coding RNA PVT1, a novel
biomarker for chronic obstructive pulmonary disease progression
surveillance and acute exacerbation prediction potentially through
interaction with microRNA-146a. J Clin Lab Anal. 2020;34(8):e23346.

48. Qian Y, Mao ZD, Shi YJ, Liu ZG, Cao Q, Zhang Q. Comprehensive
Analysis of miRNA-mRNA-lncRNA Networks in Non-Smoking and Smoking
Patients with Chronic Obstructive Pulmonary Disease. Cell Physiol
Biochem. 2018;50(3):1140-53.

49. Fan S, Ren Y, Zhang W, Zhang H, Wang C. Long non-coding maternally
expressed gene 3 regulates cigarette smoke extract-induced apoptosis,
inflammation and cytotoxicity by sponging miR-181a-2-3p in 16HBE cells.
Oncol Lett. 2021;21(1):45.

50. Zhao J, Pu J, Hao B, Huang L, Chen J, Hong W, et al. LncRNA
RP11-86H7.1 promotes airway inflammation induced by TRAPM2.5 by acting
as a ceRNA of miRNA-9-5p to regulate NFKB1 in HBECS. Sci Rep.
2020;10(1):11587.

51. Barta JA, Powell CA, Wisnivesky JP. Global Epidemiology of Lung
Cancer. Ann Glob Health. 2019;85(1).

52. Duma N, Santana-Davila R, Molina JR. Non--Small Cell Lung Cancer:
Epidemiology, Screening, Diagnosis, and Treatment. Mayo Clinic
Proceedings. 2019;94(8):1623-40.

53. Sun Q, Hao Q, Prasanth KV. Nuclear Long Noncoding RNAs: Key
Regulators of Gene Expression. Trends Genet. 2018;34(2):142-57.

54. Sanchez Calle A, Kawamura Y, Yamamoto Y, Takeshita F, Ochiya T.
Emerging roles of long non-coding RNA in cancer. Cancer Sci.
2018;109(7):2093-100.

55. Jin D, Guo J, Wu Y, Du J, Yang L, Wang X, et al. m(6)A mRNA
methylation initiated by METTL3 directly promotes YAP translation and
increases YAP activity by regulating the MALAT1-miR-1914-3p-YAP axis to
induce NSCLC drug resistance and metastasis. J Hematol Oncol.
2019;12(1):135.

56. Tang Q, Hann SS. HOTAIR: An Oncogenic Long Non-Coding RNA in Human
Cancer. Cellular Physiology and Biochemistry. 2018;47(3):893-913.

57. Jiang CY, Yang Y, Yang Y, Guo L, Huang J, Liu XR, et al. Long
Noncoding RNA (IncRNA) HOTAIR Affects Tumorigenesis and Metastasis of
Non-Small Cell Lung Cancer by Upregulating miR-61. Oncology Research.
2018;26(5):725-34.

58. Sun YJ, Li J, Chen CH. Effects of miR-221 on the apoptosis of
non-small cell lung cancer cells by lncRNA HOTAIR. European Review for
Medical and Pharmacological Sciences. 2019;23(10):4226-33.

59. Zhan YY, Abuduwaili K, Wang XL, Shen YL, Nuerlan S, Liu CL.
Knockdown of Long Non-Coding RNA HOTAIR Suppresses Cisplatin Resistance,
Cell Proliferation, Migration and Invasion of DDP-Resistant NSCLC Cells
by Targeting miR-149-5p/Doublecortin-Like Kinase 1 Axis. Cancer
Management and Research. 2020;12:7725-37.

60. Chen SS, Peng M, Zhou GZ, Pu YC, Yi MC, Zhu Y, et al. Long
non-coding RNA HOTAIR regulates the development of non-small cell lung
cancer through miR-217/DACH1 signaling pathway. European Review for
Medical and Pharmacological Sciences. 2019;23(2):670-8.

61. Qu R, Chen X, Zhang C. LncRNA ZEB1-AS1/miR-409--3p/ZEB1 feedback
loop is involved in the progression of non-small cell lung cancer.
Biochemical and Biophysical Research Communications. 2018;507(1):450-6.

62. Zhong Y, Lin H, Li Q, Liu C, Zhong L. Downregulation of long
non-coding RNA GACAT1 suppresses proliferation and induces apoptosis of
NSCLC cells by sponging microRNA-422a. Int J Mol Med. 2021;47(2):659-67.

63. Li J, Xia R, Liu T, Cai X, Geng G. LncRNA-ATB Promotes Lung Squamous
Carcinoma Cell Proliferation, Migration, and Invasion by Targeting
MicroRNA-590-5p/NF90 Axis. DNA and Cell Biology. 2020;39(3):459-73.

64. Zhang Y, Zhang Y, Zeng Q, Li C, Zhou H, Liu J, et al.
IL-1(3-Triggered Long Non-coding RNA CHRF Induces Non-Small Cell Lung
Cancer by Modulating the microRNA-489/Myd88 Axis. Journal of Cancer.
2022;13(8):2620-30.

65. Zhao L, Wang L, Wang Y, Ma P. Long non-coding RNA CCAT1 enhances
human non-small cell lung cancer growth through downregulation of
microRNA-218. Oncology Reports. 2020;43(4):1045-52.

66. Zhou Y, Shi H, Du Y, Zhao G, Wang X, Li Q, et al. lncRNA DLEU2
modulates cell proliferation and invasion of non-small cell lung cancer
by regulating miR-30c-5p/SOX9 axis. Aging-Us. 2019;11(18):7386-401.

67. Li P, Xing W, Xu J, Yuan D, Liang G, Liu B, et al. microRNA-301b-3p
downregulation underlies a novel inhibitory role of long non-coding RNA
MBNL1-AS1 in non-small cell lung cancer. Stem Cell Research \& Therapy.
2019;10.

68. Ku GW, Kang Y, Yu S-L, Park J, Park S, Jeong IB, et al. LncRNA
LINC00240 suppresses invasion and migration in non-small cell lung
cancer by sponging miR-7-5p. Bmc Cancer. 2021;21(1).

69. Liu J, Yao L, Zhang M, Jiang J, Yang M, Wang Y. Downregulation of
LncRNA-XIST inhibited development of non-small cell lung cancer by
activating miR-335/SOD2/ROS signal pathway mediated pyroptotic cell
death. Aging-Us. 2019;11(18):7830-46.

70. Lv X, Lian Y, Liu Z, Xiao J, Zhang D, Yin X. Exosomal long
non-coding RNA LINC00662 promotes non-small cell lung cancer progression
by miR-320d/E2F1 axis. Aging-Us. 2021;13(4):6010-24.

71. Wu JL, Meng FM, Li HJ. High expression of lncRNA MEG3 participates
in non-small cell lung cancer by regulating microRNA-7-5p. European
Review for Medical and Pharmacological Sciences. 2018;22(18):5938-45.

72. Yuan S, Xiang Y, Wang G, Zhou M, Meng G, Liu Q, et al.
Hypoxia-sensitive LINC01436 is regulated by E2F6 and acts as an oncogene
by targeting miR-30a-3p in non-small cell lung cancer. Molecular
Oncology. 2019;13(4):840-56.

73. Wu Z-H, Zhou J, Hu G-H, Liu J, Li W-C, Lai X-H, et al. LncRNA CASC2
inhibits lung adenocarcinoma progression through forming feedback loop
with miR-21/p53 axis. Kaohsiung Journal of Medical Sciences.
2021;37(8):675-85.

74. Qian B, Wang DM, Gu XS, Zhou K, Wu J, Zhang CY, et al. LncRNA H19
serves as a ceRNA and participates in non-small cell lung cancer
development by regulating microRNA-107. European Review for Medical and
Pharmacological Sciences. 2018;22(18):5946-53.

75. Ren J, Fu J, Ma T, Yan B, Gao R, An Z, et al. LncRNA H19-elevated
LIN28B promotes lung cancer progression through sequestering miR-196b.
Cell Cycle. 2018;17(11):1372-80.

76. Wang L, Cao L, Wen C, Li J, Yu G, Liu C. LncRNA LINC00857 regulates
lung adenocarcinoma progression, apoptosis and glycolysis by targeting
miR-1179/SPAG5 axis. Human Cell. 2020;33(1):195-204.

77. Shen Q, Jiang Y. LncRNA NNT-AS1 promotes the proliferation, and
invasion of lung cancer cells via regulating miR-129-5p expression.
Biomedicine \& Pharmacotherapy. 2018;105:176-81.

78. Chen L, Qiu CH, Chen Y, Wang Y, Zhao JJ, Zhang M. LncRNA SNHG16
drives proliferation, migration, and invasion of lung cancer cell
through modulation of miR-520/VEGF axis. European Review for Medical and
Pharmacological Sciences. 2020;24(18):9522-31.

79. Tang L, Wang S, Wang Y, Li K, Li Q. LncRNA-UCA1 regulates lung
adenocarcinoma progression through competitive binding to miR-383. Cell
Cycle. 2022.

80. Feng J, Li J, Qie P, Li Z, Xu Y, Tian Z. Long non-coding RNA
(lncRNA) PGM5P4-AS1 inhibits lung cancer progression by up-regulating
leucine zipper tumor suppressor (LZTS3) through sponging microRNA
miR-1275. Bioengineered. 2021;12(1):196-207.

81. Li H, Guo X, Li Q, Ran P, Xiang X, Yuan Y, et al. Long non-coding
RNA 1308 promotes cell invasion by regulating the miR-124/ADAM 15 axis
in non-small-cell lung cancer cells. Cancer Management and Research.
2018;10:6599-609.

82. Pan X, Chen S, Ye L, Xu S, Wang L, Sun Y. Long non-coding RNA
DLGAP1-AS1 modulates the development of non-small-cell lung cancer via
the microRNA-193a-5p/DTL axis. Laboratory Investigation. 2022.

83. Chen L, Ren P, Zhang Y, Gong B, Yu D, Sun X. Long non-coding RNA
GAS5 increases the radiosensitivity of A549 cells through interaction
with the miR-21/PTEN/Akt axis. Oncology Reports. 2020;43(3):897-907.

84. Li H, Chen S, Liu J, Guo X, Xiang X, Dong T, et al. Long non-coding
RNA PVT1-5 promotes cell proliferation by regulating miR-126/SLC7A5 axis
in lung cancer. Biochemical and Biophysical Research Communications.
2018;495(3):2350-5.

85. Zhao L, Song X, Guo Y, Ding N, Wang T, Huang L. Long non-coding RNA
SNHG3 promotes the development of non-small cell lung cancer via the
miR-1343-3p/NFIX pathway. International Journal of Molecular Medicine.
2021;48(2).

86. Wang F, Quan Q. The long non-coding RNA
SNHG4/microRNA-let-7e/KDM3A/p21 pathway is involved in the development
of non-small cell lung cancer. Molecular Therapy-Oncolytics.
2021;20:634-45.

87. Lu Q, Shan S, Li Y, Zhu D, Jin W, Ren T. Long noncoding RNA SNHG1
promotes non-small cell lung cancer progression by up-regulating MTDH
via sponging miR-145-5p. Faseb Journal. 2018;32(7):3957-67.

88. Feng T, Feng N, Zhu T, Li Q, Zhang Q, Wang Y, et al. A SNP-mediated
lncRNA (LOC146880) and microRNA (miR-539-5p) interaction and its
potential impact on the NSCLC risk. Journal of Experimental \& Clinical
Cancer Research. 2020;39(1).

89. Papi A, Brightling C, Pedersen SE, Reddel HK. Asthma. The Lancet.
2018;391(10122):783-800.

90. Nanda A, Wasan AN. Asthma in Adults. Medical Clinics of North
America. 2020;104(1):95-108.

91. Serebrisky D, Wiznia A. Pediatric Asthma: A Global Epidemic. Ann
Glob Health. 2019;85(1).

92. Li X, Ye S, Lu Y. Long non-coding RNA NEAT1 overexpression
associates with increased exacerbation risk, severity, and inflammation,
as well as decreased lung function through the interaction with
microRNA-124 in asthma. J Clin Lab Anal. 2020;34(1):e23023.

93. Ma L, Zhang Q, Hao J, Wang J, Wang C. LncRNA PVT1 exacerbates the
inflammation and cell-barrier injury during asthma by regulating
miR-149. J Biochem Mol Toxicol. 2020;34(11):e22563.

94. Liang Z, Tang F. The potency of lncRNA MALAT1/miR-155/CTLA4 axis in
altering Th1/Th2 balance of asthma. Biosci Rep. 2020;40(2).

95. Boulet LP. Airway remodeling in asthma: update on mechanisms and
therapeutic approaches. Current Opinion in Pulmonary Medicine.
2018;24(1):56-62.

96. Wang X, Xu R, Chi D, Dai C, Sheng M. Role of NEAT1/MiR-9-5p/SLC26A2
Pathway on Human Airway Smooth Muscle Cell. Yonsei Med J.
2021;62(9):858-67.

97. Lin L, Li Q, Hao W, Zhang Y, Zhao L, Han W. Upregulation of LncRNA
Malat1 Induced Proliferation and Migration of Airway Smooth Muscle Cells
via miR-150-eIF4E/Akt Signaling. Front Physiol. 2019;10:1337.

98. Zhang X-y, Tang X-y, Li N, Zhao L-m, Guo Y-l, Li X-s, et al. GAS5
promotes airway smooth muscle cell proliferation in asthma via
controlling miR-10a/BDNF signaling pathway. Life Sciences.
2018;212:93-101.

99. Wang W-L, Luo X-M, Zhang Q, Zhu H-Q, Chen G-Q, Zhou Q. The lncRNA
PVT1/miR-590-5p/FSTL1 axis modulates the proliferation and migration of
airway smooth muscle cells in asthma. Autoimmunity. 2021;54(3):138-47.

100. Lin L, Li Q, Hao W, Zhang Y, Zhao L, Han W. Upregulation of LncRNA
Malat1 Induced Proliferation and Migration of Airway Smooth Muscle Cells
via miR-150-eIF4E/Akt Signaling. Frontiers in Physiology. 2019;10.

101. Fan E, Brodie D, Slutsky AS. Acute Respiratory Distress Syndrome:
Advances in Diagnosis and Treatment. Jama. 2018;319(7):698-710.

102. Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, et al.
Epidemiology, Patterns of Care, and Mortality for Patients With Acute
Respiratory Distress Syndrome in Intensive Care Units in 50 Countries.
Jama. 2016;315(8):788-800.

103. Matthay MA, Zemans RL, Zimmerman GA, Arabi YM, Beitler JR, Mercat
A, et al. Acute respiratory distress syndrome. Nat Rev Dis Primers.
2019;5(1):18.

104. Huang X, Xiu H, Zhang S, Zhang G. The Role of Macrophages in the
Pathogenesis of ALI/ARDS. Mediators Inflamm. 2018;2018:1264913.

105. Vassiliou AG, Kotanidou A, Dimopoulou I, Orfanos SE. Endothelial
Damage in Acute Respiratory Distress Syndrome. Int J Mol Sci.
2020;21(22).

106. Vergadi E, Vaporidi K, Tsatsanis C. Regulation of Endotoxin
Tolerance and Compensatory Anti-inflammatory Response Syndrome by
Non-coding RNAs. Front Immunol. 2018;9:2705.

107. Zhao G, Su Z, Song D, Mao Y, Mao X. The long noncoding RNA MALAT1
regulates the lipopolysaccharide-induced inflammatory response through
its interaction with NF-\selectlanguage{greek}κ\selectlanguage{english}B. FEBS Lett. 2016;590(17):2884-95.

108. Wang H, Song S, Mu X. Long non-coding RNA HOTAIR knockdown
alleviates lipopolysaccharide-induced acute respiratory distress
syndrome and the associated inflammatory response by modulating the
microRNA-30a-5p/PDE7A axis. Exp Ther Med. 2021;22(4):1160.

109. Lederer DJ, Martinez FJ. Idiopathic Pulmonary Fibrosis. New England
Journal of Medicine. 2018;378(19):1811-23.

110. Desai O, Winkler J, Minasyan M, Herzog EL. The Role of Immune and
Inflammatory Cells in Idiopathic Pulmonary Fibrosis. Front Med
(Lausanne). 2018;5:43.

111. Maher TM, Strek ME. Antifibrotic therapy for idiopathic pulmonary
fibrosis: time to treat. Respir Res. 2019;20(1):205.

112. Rout-Pitt N, Farrow N, Parsons D, Donnelley M. Epithelial
mesenchymal transition (EMT): a universal process in lung diseases with
implications for cystic fibrosis pathophysiology. Respir Res.
2018;19(1):136.

113. Liu Y, Li Y, Xu Q, Yao W, Wu Q, Yuan J, et al. Long non-coding
RNA-ATB promotes EMT during silica-induced pulmonary fibrosis by
competitively binding miR-200c. Biochimica et Biophysica Acta (BBA) -
Molecular Basis of Disease. 2018;1864(2):420-31.

114. Xu Q, Cheng D, Liu Y, Pan H, Li G, Li P, et al. LncRNA-ATB
regulates epithelial-mesenchymal transition progression in pulmonary
fibrosis via sponging miR-29b-2-5p and miR-34c-3p. J Cell Mol Med.
2021;25(15):7294-306.

115. Xu H, Chen Y, Zhuang J, Zhu S, Xu B, Hong J. The role and mechanism
of lncRNA NEAT1 in the fibrosis of pulmonary epithelial cell. Molecular
\& Cellular Toxicology. 2020;16(2):185-91.

116. Li X, Yu T, Shan H, Jiang H, Sun J, Zhao X, et al. lncRNA PFAL
promotes lung fibrosis through CTGF by competitively binding miR-18a.
Faseb j. 2018;32(10):5285-97.

117. Jiang H, Chen Y, Yu T, Zhao X, Shan H, Sun J, et al. Inhibition of
lncRNA PFRL prevents pulmonary fibrosis by disrupting the miR-26a/smad2
loop. Am J Physiol-Lung Cell Mol Physiol. 2018;315(4):L563-L75.

118. Liu X, Gao S, Xu H. lncRNAPCAT29 inhibits pulmonary fibrosis via
the TGF-\selectlanguage{greek}β\selectlanguage{english}1-regulated RASAL1/ERK1/2 signal pathway. Mol Med Rep.
2018;17(6):7781-8.

119. Wu QY, Jiao BY, Gui WW, Zhang QY, Wang F, Han L. Long non-coding
RNA SNHG1 promotes fibroblast-to-myofibroblast transition during the
development of pulmonary fibrosis induced by silica particles exposure.
Ecotoxicology and Environmental Safety. 2021;228.

120. Deng W, Zhang Y, Fang P, Shi H, Yang S. Silencing lncRNA Snhg6
mitigates bleomycin-induced pulmonary fibrosis in mice via
miR-26a-5p/TGF-\selectlanguage{greek}β\selectlanguage{english}1-smads axis. Environ Toxicol. 2022.

121. Ballester B, Milara J, Cortijo J. Idiopathic Pulmonary Fibrosis and
Lung Cancer: Mechanisms and Molecular Targets. Int J Mol Sci.
2019;20(3).\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Fig/Fig}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

