Alternative splicing: a bridge connecting NAFLD and HCC

Non-alcoholic fatty liver disease (NAFLD) is becoming the most important risk factor for hepatocellular carcinoma (HCC). Understanding the progression of benign diseases to HCC is crucial for early prevention and reversal of malignant transformation. Alternative splicing (AS) of RNA plays a role in the pathogenicity, initiation, and transformation of liver disease. We summarize the changes or mutations in the activity of splicing factors in NAFLD and HCC, as well as the impact of AS mediated by epigenetic modifications such as DNA methylation, RNA methylation, histone modification, and protein phosphorylation on liver cell fate. We also summarize therapeutic methods and drugs that are helpful for treating NAFLD, HCC, and the early stages of NAFLD progression to HCC.