The emerging roles of m⁶A modification in liver carcinogenesis

The 'epitranscriptome', a collective term for chemical modifications that influence the structure, metabolism, and functions of RNA, has recently emerged as vitally important for the regulation of gene expression. N⁶-methyladenosine (m⁶A), the most prevalent mammalian mRNA internal modification, has been demonstrated to have a pivotal role in almost all vital bioprocesses, such as stem cell self-renewal and differentiation, heat shock or DNA damage response, tissue development, and maternal-to-zygotic transition. Hepatocellular carcinoma (HCC) is prevalent worldwide with high morbidity and mortality because of late diagnosis at an advanced stage and lack of effective treatment strategies. Epigenetic modifications including DNA methylation and histone modification have been demonstrated to be crucial for liver carcinogenesis. However, the role and underlying molecular mechanism of m⁶A in liver carcinogenesis are mostly unknown. In this review, we summarize recent advances in the m⁶A region and how these new findings remodel our understanding of m⁶A regulation of gene expression. We also describe the influence of m⁶A modification on liver carcinoma and lipid metabolism to instigate further investigations of the role of m⁶A in liver biological diseases and its potential application in the development of therapeutic strategies.