Unveiling the hidden regulators: how post-translational modifications influence the progression and treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a common and aggressive primary liver cancer. Due to its high incidence and fatality rates, it poses a serious threat to global public health. Protein post-translational modifications (PTMs) are crucial regulatory mechanisms that occur after translation and fine-tune cellular functions. Common PTM types-including phosphorylation, ubiquitination, acetylation, methylation, glycosylation, ubiquitin-like modifications (such as UFMylation and SUMOylation), and Lactylation-affect protein activity, stability, subcellular localization, and interaction networks. These modifications dynamically regulate various biological processes in response to internal and external stimuli. Dysregulated PTMs have been intimately associated with the development, spread, and resistance to treatment of HCC in the setting of cancer. This review provides new insights into the molecular mechanisms underlying HCC by systematically examining the roles of PTMs. It also seeks to inform therapeutic strategies and improve diagnosis and prognostic assessment.