From inflammation to carcinogenesis: MiRNA regulates epithelial-mesenchymal transition to facilitate malignant progression of gastric precancerous lesions.

The process of chronic gastritis transforming into gastric cancer (GC) follows the classic Correa cascade, with persistent inflammation driving the stepwise transition from normal gastric mucosa through superficial gastritis, atrophic gastritis, intestinal metaplasia, dysplasia, and ultimately carcinoma. Among these stages, intestinal metaplasia and dysplasia occurring on an atrophic mucosal background are widely regarded as the most common gastric precancerous lesions (GPL) because of their pronounced carcinogenic risk. Chronic inflammation can induce epithelial-mesenchymal transition (EMT), thereby accelerating gastric malignant progression. In the GPL stage, the inflammatory gastric microenvironment commonly induces partial EMT (pEMT); importantly, this state is partly reversible and may be amenable to intervention to slow disease progression. As lesions advance, epithelial cells more fully undergo EMT, acquiring greater motility, invasiveness, and metastatic capability, which increases susceptibility to malignant conversion. MicroRNAs (miRNAs) are key molecular regulators in the transition from chronic gastritis to GC through EMT modulation. This review comprehensively discusses inflammation-driven EMT activation and functionally classifies pro-EMT oncomiRNAs (e.g., miR-21, miR-155) and anti-EMT tumor-suppressive miRNAs (e.g., miR-200 family, let-7 family, miR-34a), delineating a complex crosstalk network among inflammation, miRNA, and EMT. We further evaluate miRNAs as non-invasive biomarkers for early detection and prognosis of GPL and discuss emerging therapeutic strategies targeting the miRNA-EMT axis, including nanoparticle- or exosome-based delivery systems, miRNA antagonists, and miRNA sponges. Nevertheless, clinical application of circulating miRNAs remains limited by insufficient assay standardization and validation, incomplete target specificity, off-target effects, suboptimal delivery efficiency, and a lack of large-scale clinical evidence. By integrating molecular mechanisms and transformation status of miRNA-EMT axis in GPL, this review provides new insights for precision prevention and targeted intervention in gastric carcinogenesis.