The Role of Mitochondrial MicroRNAs in Hepatocarcinogenesis: Mechanisms, Implications, and Therapeutic Prospects
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Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with limited therapeutic options and poor prognosis. Emerging evidence highlights mitochondrial microRNAs (mt-miRNAs), a novel subclass of non-coding RNAs localized within mitochondria, as critical regulators of mitochondrial function and cellular metabolism in hepatocarcinogenesis. Mt-miRNAs modulate key processes including mitochondrial biogenesis, dynamics, apoptosis, and energy metabolism, influencing tumor initiation and progression. Dysregulation of mt-miRNAs alters mitochondrial homeostasis and contributes to HCC pathogenesis by affecting oncogene and tumor suppressor networks. Recent advances have demonstrated the potential of mt-miRNAs as diagnostic biomarkers and therapeutic targets, with innovative mitochondria-targeted delivery systems showing promise in preclinical models. However, challenges related to mt-miRNA biogenesis, mitochondrial localization mechanisms, and delivery specificity remain. This review provides a comprehensive overview of the mechanistic roles of mt-miRNAs in liver cancer, their implications for disease progression, and emerging therapeutic strategies, highlighting future research directions that could enable translation into clinical applications.