MicroRNAs as Emerging Regulators of Signaling in the Tumor Microenvironment

Abstract

A myriad of signaling molecules in a heuristic network of the tumor microenvironment (TME) pose a challenge and an opportunity for novel therapeutic target identification in human cancers. MicroRNAs (miRs), due to their ability to affect signaling pathways at various levels, take a prominent space in the quest of novel cancer therapeutics. The role of miRs in cancer initiation, progression, as well as in chemoresistance, is being increasingly investigated. The canonical function of miRs is to target mRNAs for post-transcriptional gene silencing, which has a great implication in first-order regulation of signaling pathways. However, several reports suggest that miRs also perform non-canonical functions, partly due to their characteristic non-coding small RNA nature. Examples emerge when they act as ligands for toll-like receptors or perform second-order functions, e.g., to regulate protein translation and interactions. This review is a compendium of recent advancements in understanding the role of miRs in cancer signaling and focuses on the role of miRs as novel regulators of the signaling pathway in the TME.

Exosomes derived from human amniotic epithelial cells accelerate diabetic wound healing via PI3K-AKT-mTOR-mediated promotion in angiogenesis and fibroblast function

“…The group of miRNAs is a short non-coding RNA with a length of about 20–24 nucleotides and regulates nearly one-third of human genes via binding to the 3’ untranslated regions (3’ UTRs) of their target mRNAs [ 25 ]. A large number of studies have shown that miRNAs are the primary effective cargo of exosomes [ 11 , 18 , 26 , 27 ].…”

Serum exosomal microRNA‐766‐3p expression is associated with poor prognosis of esophageal squamous cell carcinoma

“…MicroRNAs are small noncoding RNAs that are thought to play important roles in many biological pathways 8 . Altered expression of miRNAs is involved in the regulation of crucial pathological processes in disease progression 9,10 . Exosomes are small membrane vesicles of endocytic origin that are released into the extracellular environment 11 .…”

MicroRNA‑138 modulates glioma cell growth, apoptosis and invasion through the suppression of the AKT/mTOR signalling pathway by targeting CREB1

“…miRNAs have been reported to participate in several malignant biological behaviours, including cell proliferation, metabolism and differentiation, at the post-transcriptional level ( 23 , 24 ). Mutations affecting miRNAs or their functional interactions with oncogenes and tumour suppressors may mediate tumourigenesis ( 25 ).…”