MicroRNAs in HCC: regulatory roles and therapeutic potential

Hepatocellular carcinoma (HCC) ranks among the malignancies with the highest mortality rates worldwide. Owing to the lack of effective diagnostic and therapeutic strategies, patient prognosis generally remains poor. MicroRNAs (miRNAs) function as both oncogenes and tumor suppressors, exerting precise regulatory control over diverse biological behaviors in HCC through multiple pathways. This review summarizes how miRNAs modulate the activation of critical signaling cascades, including the Wnt/β-catenin, PI3K/AKT/mTOR, TGF-β/Smad, and MAPK/ERK pathways, by targeting numerous genes. Furthermore, miRNAs contribute to HCC pathogenesis and progression by reshaping the tumor microenvironment and inducing metabolic reprogramming. Given their pivotal regulatory roles in HCC, we also comprehensively evaluate the diagnostic and therapeutic potential of miRNAs as clinical targets and highlight the major challenges currently impeding their translation.