MicroRNAs as Mediators of Mechanotransduction: from Fundamental Mechanisms to Therapeutic Applications.

MicroRNAs (miRNAs) are key gene expression regulators involved in essential cellular processes. They also mediate mechanotransduction, translating mechanical cues like shear stress, tensile forces, and ECM stiffness into intracellular signals. This review examines the bidirectional relationship between mechanical stimuli and miRNAs: how mechanical cues regulate miRNA biogenesis and how specific miRNAs (e.g., miR-10a, miR-19a, miR-143/145) modulate Hippo-YAP/TAZ and Wnt pathways to control cytoskeletal dynamics, proliferation, differentiation, and apoptosis. Dysregulation of these mechanosensitive miRNAs is implicated in fibrosis, cancer metastasis, cardiovascular diseases, and musculoskeletal disorders, where disrupted mechanical signaling affects tissue homeostasis. We also explore the therapeutic potential of targeting the miRNA-mechanical axis, including miRNA replacement for downregulated miRNAs (e.g., miR-29) and antagomiRs to inhibit pathogenic miRNAs (e.g., miR-21). This review emphasizes the central role of miRNAs in mechanobiology and their potential for novel diagnostic and therapeutic applications across diverse human diseases.