Epitranscriptomic modifications in programmed cell death: mechanistic insights and implications for liver diseases.

Epitranscriptomic modifications, as a dynamic and reversible system of chemical modifications, have emerged as a key regulatory hub for programmed cell death (PCD) by finely modulating the RNA metabolic network. During the pathological progression of liver diseases, aberrant alterations in epitranscriptomic modifications can disrupt the dynamic equilibrium of PCD signaling pathways, leading to excessive cell death or abnormal survival of hepatocytes, thereby driving the development of metabolic dysfunction-associated steatotic liver disease (MASLD), viral hepatitis, alcohol-associated liver disease (ALD), hepatic fibrosis, and hepatocellular carcinoma (HCC). A thorough investigation into the molecular mechanisms of epitranscriptomic modifications in PCD pathways and their roles in liver diseases not only aids in elucidating the pathogenesis of liver disorders but also holds the potential to provide new biomarkers and therapeutic targets for the diagnosis, prognosis, and treatment of liver diseases. This review systematically summarizes the molecular mechanisms of epitranscriptomic modifications, delves into the complex regulatory networks between epitranscriptomic modifications and PCD, elaborates on their roles in liver diseases, and provides a comprehensive overview of current drugs targeting epitranscriptomic modifications. These insights offer new treatment ideas for liver diseases and new directions for precision medicine research.