Background
Osteosarcoma (OS) is the most prevalent primary malignant bone neoplasm
causing substantial morbidity in adolescents and children [1]. It
originates from mesenchymal cells and is characterized by rapid
infiltrating growth, early lung metastasis and a high recurrence rate
[2]. Studies have shown that the overall 5-year survival rate of
patients with localized OS ranges between 65 ~ 75% and
is only 20% for those with recurrent and metastatic tumors [3].
Despite advances in OS treatment approaches such as adjuvant
chemotherapy and surgical resection, the survival rates have plateaued
in the last 3 decades and are less than satisfactory [4]. Indeed, no
specific diagnostic and prognostic biomarkers for OS have been found.
Consequently, molecular studies aiming to identify promising therapeutic
targets for OS are urgently needed. Circular RNAs (circRNAs) regulate
various functions in eukaryotic cells [5]. Based on the order of
splicing events and different intermediates, two mechanisms exist for
the biogenesis of circRNAs: canonical spliceosome induced splicing and
noncanonical lariat splicing [6, 7]. Accumulating studies have shown
that circRNAs modulate diverse physiological and pathophysiological
processes by sponging microRNAs (miRNAs), interacting with RNA binding
proteins, and modulating epigenetic, transcriptional, or translational
alterations in target genes as well [8–11]. Abnormal circRNA
expression has been found to correlate with the pathogenesis of various
cancers and to exert essential regulatory effects on gene expression,
cell invasion, cell cycle progression, migration, apoptosis, and
proliferation [12–14]. Moreover, circRNAs are thought to possess
high diagnostic and therapeutic potential given their structural
stability, evolutionary conservation, abundance and organ specificity
[15, 16]. However, to date, the roles of circRNAs in OS are not
clearly known.
This study evaluated the expression profiles of circRNAs in OS tissues
using high-throughput sequencing. We found a novel circRNA, designated
circ_001722, significantly upregulated in OS tissues and cells. Our
experimental results indicated that circ_001722 exerted pro-oncogenic
effects on OS proliferation and invasion through
circ_001722/miR-204-5p/RUNX2 Axis. This preliminary study revealed that
circ_001722 is a potential therapeutic target for OS.