Dualistic Roles of MiR-215 in Digestive System Disorders: From Physiology to Pathology

MicroRNA-215 (miR-215), a highly conserved non-coding small molecule, plays a significant regulatory role in the maintenance of cellular homeostasis, tissue and organ development, and the pathogenesis of various diseases. In recent years, accumulating evidence has revealed that miR-215 is extensively and complexly involved in digestive system diseases, drawing considerable attention due to its aberrant expression and functional diversity across multiple digestive organs. Notably, miR-215 can exert diametrically opposing biological functions in different digestive organs, and even within the same organ under distinct pathological contexts, underscoring its unique property as a “dual-functional small molecule” and providing an ideal paradigm for deciphering the regulatory complexity of microRNA networks. This review systematically summarizes the discovery and sequence conservation features of miR-215, with a particular focus on its differential expression patterns in major digestive organs. We further dissect the molecular mechanisms underlying its pathological context-dependent functional switching in intestinal disorders, gastric cancer, and hepatic lesions, and evaluate its potential utility as a biomarker for the diagnosis and prognosis of digestive tract diseases. Collectively, this review aims to provide a theoretical foundation and novel insights for the early detection, prognostic assessment, and precision-targeted therapy of digestive system disorders.