Abstract
BACKGROUND AND OBJECTIVE: MicroRNAs (miRNAs or miRs) are critical epigenetic regulators in gastric carcinogenesis; however, to date, comprehensive analyses of their stage-specific dysregulation and clinical utility are limited. This review synthesized evidence on miRNA dysregulation throughout the gastritis-metaplasia-cancer cascade to assess the diagnostic and therapeutic potential of miRNAs. Research challenges are also discussed. METHODS: A narrative overview was conducted based on systematic searches of the PubMed and Web of Science databases (from 1993-2025.03), focusing on high-impact studies on miRNA expression, and their functional mechanisms and clinical utility in gastric precancerous and cancerous lesions. KEY CONTENT AND FINDINGS: Stage-specific miRNA dysregulation contributes to gastric disease progression. In chronic gastritis (CG), miR-155 and let-7b regulate inflammation, while miR-92a-1-5p and miR-296-5p participate in intestinal metaplasia (IM) by modulating CDX2/FOXD1 and ERK signaling. In gastric cancer (GC), miR-21 and miR-375 regulate proliferation and apoptosis. Clinically, circulating miRNA panels (e.g., miR-4257, miR-6785-5p, and miR-187-5p) enhance early detection, while miR-125a-5p boosts the trastuzumab response via ERBB2 targeting. Despite progress, challenges remain in the mechanistic and clinical validation of miRNAs. Integrating multi-omics and machine learning may optimize miRNA-based diagnostics and therapeutics for precision medicine. CONCLUSIONS: This review highlights miRNAs as pivotal regulators in gastric carcinogenesis and promising precision medicine tools. The study findings will promote the standardization of profiling methods and accelerate translational research, both of which are essential to the advancement of GC diagnostic and therapeutic strategies.