Non-Coding RNAs in Gastric Cancer: From Malignant Hallmarks to Clinical Applications.

Di Chen,Xin Jiang,Mengmeng Wang,Honglu Yu,Zhifan Xiong,Shuai Ping,Lina Xiong,Li Zhang,Yushuang Xu

doi:10.3389/fcell.2021.732036

Abstract

Gastric cancer (GC) is one of the most lethal malignancies worldwide. However, the molecular mechanisms underlying gastric carcinogenesis remain largely unknown. Over the past decades, advances in RNA-sequencing techniques have greatly facilitated the identification of various non-coding RNAs (ncRNAs) in cancer cells, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Accumulating evidence has revealed that ncRNAs are essential regulators in GC occurrence and development. However, ncRNAs represent an emerging field of cancer research, and their complex functionality remains to be clarified. Considering the lack of viable biomarkers and therapeutic targets in GC, further studies should focus on elucidating the intricate relationships between ncRNAs and GC, which can be translated into clinical practice. In this review, we summarize recent research progress on how ncRNAs modulate the malignant hallmarks of GC, especially in tumor immune escape, drug resistance, and stemness. We also discuss the promising applications of ncRNAs as diagnostic biomarkers and therapeutic targets in GC, aiming to validate their practical value for clinical treatment.

Highlights

Gastric cancer (GC) is one of the most commonly diagnosed malignancies, with over one million estimated new cases annually, and remains the third most common cause of cancerrelated deaths worldwide (Bray et al, 2018)
We summarize the common deregulation of Non-coding RNAs (ncRNAs) and their roles and molecular mechanisms in regulating the malignant hallmarks of GC
Downregulation of FENDRR decreases drug resistant of multidrug resistance (MDR) GC cells by performing an enhancer-like role and sponging miR-4700-3p to promote FOXC2 expression High levels of circMCTP2 sensitize GC cells to CDDP through miR-99a5p-mediated induction of MTMR3 expression Knockdown of circAKT3 effectively increases CDDP sensitivity in GC cells via targeting the miR-198/PIK3R1 axis CircCUL2 functions as a regulator of cisplatin sensitivity via miR-142-3p/ ROCK2-mediated autophagy activation Silencing of circDONSON reduces CDDP resistance of GC cells through modulating the miR-802/BMI1 axis

Summary

Introduction

Gastric cancer (GC) is one of the most commonly diagnosed malignancies, with over one million estimated new cases annually, and remains the third most common cause of cancerrelated deaths worldwide (Bray et al, 2018). Downregulation of FENDRR decreases drug resistant of MDR GC cells by performing an enhancer-like role and sponging miR-4700-3p to promote FOXC2 expression High levels of circMCTP2 sensitize GC cells to CDDP through miR-99a5p-mediated induction of MTMR3 expression Knockdown of circAKT3 effectively increases CDDP sensitivity in GC cells via targeting the miR-198/PIK3R1 axis CircCUL2 functions as a regulator of cisplatin sensitivity via miR-142-3p/ ROCK2-mediated autophagy activation Silencing of circDONSON reduces CDDP resistance of GC cells through modulating the miR-802/BMI1 axis Li et al revealed that miR-20a-5p promotes GC cell proliferation by modulating WTX expression to affect PI3K/AKT/mTOR pathway activity (Li J. et al, 2020).

Results

Conclusion