1.1.1.3. Exosomal miRNAs and autophagy
Autophagy is a catabolic process that removes damaged or redundant
macromolecules and organelles to maintain homeostasis and metabolic
adequacy [78]. This process is involved in escalating tumor
resistance against therapy and increasing tumor growth, as well as
upregulating autophagy frequently occurring leading to cell survival and
high energy supply during cancer initiation [36, 79, 80]. During a
phenomenon called cytoprotective autophagy a process caused by high
levels of autophagy and the creation of hypoxic TME, resulting in
oxidative stress, ultimately delays apoptosis and subsequently
contributes to treatment resistance [81, 82]. Upregulation of
exosomes and autophagy can act to induce an adaptive response under
cellular stress conditions in cancer cells [36]. Exosomes released
from cancer cells can induce the construction of reactive oxygen species
(ROS) and stimulate the secretion of tumor growth factors by
upregulation of autophagy in target cells [83]. Moreover, during a
drug treatment regimen, exosomes derived from cancer cells cause a
resistant phenotype in target cells by upregulation of cytoprotective
autophagy [84]. Exosomal miRNAs can control autophagy and play a
role as mediators in therapeutic resistance [36, 85, 86]. For
example, cisplatin-resistant non-small cell lung cancer (NSCLC) cells
secreted exosomal miR-425-3p, which targeted the AKT1/mTOR signaling
pathway and subsequently led to the upregulated autophagy activity and
reduced cisplatin treatment outcomes [87].