Epigenetic and post-translational modifications in ferroptosis regulation and hepatocellular carcinoma: New frontiers in therapeutic targeting.

Hepatocellular carcinoma (HCC), the predominant kind of liver cancer, continues to be a significant contributor to cancer-related deaths globally, influenced by intricate molecular processes and strong resistance to existing chemotherapy. Iron-dependent lipid peroxidation induces ferroptosis, a controlled form of cell death that plays a crucial role in inhibiting tumor growth and treatment resistance in HCC. Recent research has shown that epigenetic modifications, such as DNA methylation, histone modifications, regulation by non-coding RNAs (ncRNAs), and post-translational modification (PTM) like ubiquitination, phosphorylation, acetylation, and methylation, play a crucial role in fine-tuning ferroptosis. These alterations alter the structure of chromatin, gene expression, and protein function, thereby affecting cancer cells' fate. This review emphasizes the complex functions of epigenetic and post-translational alterations in controlling ferroptosis, providing valuable insights into their potential as therapeutic targets in HCC. The unraveling of these pathways offers a significant opportunity for novel therapies targeted at surmounting drug resistance and enhancing patient outcomes in liver cancer.