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

胃癌上皮间质转化——microRNA的作用

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Abstract

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.

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