Central role of HDAC1 in modulating key oncogenic pathways in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) represents a major cause of cancer-related mortality worldwide, with epigenetic dysregulation contributing substantially to alterations in gene expression without changes in the underlying DNA sequence. HDAC1 has emerged as an important epigenetic regulator within this landscape. Its overexpression has been reported in multiple patient cohorts and has been associated with unfavorable clinical outcomes. The purpose of the present review is to summarize the role of HDAC1 in HCC, with a particular focus on its regulatory mechanisms, expression patterns, and therapeutic implications. We highlight the multilayered regulatory networks governing HDAC1, including activation by transcription factors, interactions with chromatin cofactors, and regulation by non-coding RNAs at transcriptional, post-transcriptional, and post-translational levels. HDAC1 contributes to the regulation of key cellular processes, such as cell growth, evasion of apoptosis, and altered metabolism, by modulating oncogenic and tumor-suppressive signaling pathways. Finally, we examine various therapeutic interventions that target or modulate HDAC1, including synthetic small-molecule inhibitors, plant-derived compounds, multivalent hybrids, peptide therapeutics, and RNA interference techniques, emphasizing their reported mechanisms and epigenetic effects.