Epigenetic regulation of miRNA genes in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a highly aggressive malignancy whose molecular basis is shaped in large part by epigenetic control of microRNA (miRNA) expression. DNA methylation, histone modification and chromatin remodelling dynamically silence tumour-suppressive miRNAs and de-repress oncogenic ones, driving HCC initiation, progression and therapy resistance; non-coding RNAs and RNA-binding proteins add a further layer of cross-regulation. This review synthesises current mechanistic and clinical evidence on epigenetic–miRNA crosstalk in HCC, with particular attention to points of disagreement between studies, quantitative diagnostic performance of circulating miRNA biomarkers, and the practical barriers — delivery, immunogenicity, and disappointing early-phase trial outcomes — that have so far limited miRNA-directed therapeutics in the clinic. We conclude by outlining the validation and translational steps needed before epigenetically informed miRNA biomarkers and therapies can be adopted in HCC management.