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

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.

Keywords: biological functions; biomarker; gastric cancer; non-coding RNAs; targeted therapy.

FIGURE 1

Biogenesis and function of miRNA, lncRNA and circRNA. (A) MiRNAs are processed from stem-loop structures of longer RNA transcripts. Mature miRNAs are loaded into the RNA-induced silencing complex (RISC) to modulate target mRNA expression by degradation or translational repression. (B) Most lncRNAs transcribed by RNA polymerase II are polyadenylated at 3′, 5′ capped and spliced. LncRNAs act as decoys or sponges for transcription factors or miRNAs and serve as regulatory molecules in epigenetic gene regulation, splicing, mRNA stability, and translation. (C) The majority of circRNAs are formed by back-splicing of precursor mRNAs (pre-mRNAs). CircRNAs exert their function via various mechanisms, including miRNA sponging, translation into proteins, interacting with proteins, and regulating their function.

FIGURE 2

The role of ncRNAs in regulating the malignant hallmarks of GC. Selected examples of ncRNAs and their molecular mechanisms in modulating the malignant hallmarks of GC, including cell proliferation, resistance to cell death, invasion and metastasis, angiogenesis, tumor-promoting inflammation, tumor immune escape, stemness, and therapy resistance.