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.
Maurya et al. (Mon,) studied this question.