Insight into the regulatory mechanism of mA modification: From MAFLD to hepatocellular carcinoma.

In recent years, there has been a significant increase in the incidence of metabolic-associated fatty liver disease (MAFLD), which has been attributed to the increasing prevalence of type 2 diabetes mellitus (T2DM) and obesity. MAFLD affects more than one-third of adults worldwide, making it the most prevalent liver disease globally. Moreover, MAFLD is considered a significant risk factor for hepatocellular carcinoma (HCC), with MAFLD-related HCC cases increasing. Approximately 1 in 6 HCC patients are believed to have MAFLD, and nearly 40 % of these HCC patients do not progress to cirrhosis, indicating direct transformation from MAFLD to HCC. N6-methyladenosine (mA) is commonly distributed in eukaryotic mRNA and plays a crucial role in normal development and disease progression, particularly in tumors. Numerous studies have highlighted the close association between abnormal mA modification and cellular metabolic alterations, underscoring its importance in the onset and progression of MAFLD. However, the specific impact of mA modification on the progression of MAFLD to HCC remains unclear. Can targeting mA effectively halt the progression of MAFLD-related HCC? In this review, we investigated the pivotal role of abnormal mA modification in the transition from MAFLD to HCC, explored the potential of mA modification as a therapeutic target for MAFLD-related HCC, and proposed possible directions for future investigations.