# Gastric Cancer Epithelial-Mesenchymal Transition-The Role of Micro-RNA

## TL;DR

This paper reviews how microRNAs regulate epithelial-mesenchymal transition in gastric cancer, influencing tumor spread and treatment resistance.

## Contribution

The study systematically synthesizes current evidence on miRNA networks regulating EMT in gastric cancer and their roles in the tumor microenvironment.

## Key findings

- Downregulated tumor-suppressive miRNAs like miR-34a and miR-200 family reverse EMT in preclinical models.
- Upregulated oncomiRs such as miR-21 and miR-17-5p reinforce EMT pathways and promote tumor progression.
- EMT-related miRNAs are detectable in circulation and correlate with metastasis, prognosis, and therapy response.

## Abstract

Epithelial-mesenchymal transition (EMT) drives invasion, metastasis, immuno-evasion, and therapy resistance in gastric cancer, regulated by a complex network of microRNAs. This review aimed to synthesize current evidence on EMT-related miRNAs and their regulatory roles within tumor cells and the tumor microenvironment, including CAFs, TAMs, TANs, NK cells, and systemic inflammatory mediators. Downregulated tumor-suppressive miRNAs and upregulated oncomiRs form interconnected networks that stabilize EMT, promote tumor plasticity, and accelerate disease progression. Many of these miRNAs are detectable in circulation and correlate with metastasis, prognosis, and therapy response, highlighting their potential as diagnostic, prognostic, and therapeutic biomarkers. Translational studies are needed to validate these candidates, integrate them with molecular subtypes, and guide pathway-directed interventions to improve patient outcomes.

Epithelial-mesenchymal transition (EMT) is a key driver of invasion, metastasis, and treatment resistance in gastric cancer, yet its post-transcriptional regulation by microRNAs (miRNAs) is not fully delineated. We performed a structured literature search in PubMed, Web of Science, and Scopus for studies evaluating miRNAs in relation to EMT in gastric cancer and synthesised tumor-intrinsic, microenvironmental, and circulating EMT-related miRNA networks. Downregulated, predominantly tumor-suppressive miRNAs, including miR-34a, miR-200 family, miR-148a, miR-204, miR-30a, miR-101, miR-218, miR-26a, miR-375, miR-506, and others, converge on EMT transcription factors and pathways such as ZEB1/2, Snail, TGF-β/SMAD, Wnt/β-catenin, c-Met, and PI3K/AKT, and their restoration reverses EMT phenotypes in preclinical models. Upregulated oncomiRs, such as miR-21, miR-17-5p, miR-106b-5p, miR-23a, miR-130a-3p, miR-196a-5p, miR-181a, miR-616-3p, miR-301a-3p, miR-150, miR-27a-3p and miR-192/215, target tumor suppressors and reinforce these pathways. Cancer-associated fibroblast, macrophage, neutrophil, and natural killer cell-derived miRNAs, together with systemic indices such as the neutrophil-to-lymphocyte ratio and mediators like FAM3C, add microenvironmental layers of EMT regulation. Several EMT-related miRNAs show consistent associations with invasion, metastasis, peritoneal dissemination, prognosis, and chemoresistance, and many are detectable in circulation. Overall, EMT-related miRNAs orchestrate gastric cancer cell plasticity and tumor-microenvironment crosstalk and represent promising biomarker and therapeutic candidates that warrant validation in prospective, subtype-stratified, and translational studies.