Role of RNA modifications in carcinogenesis and carcinogen damage response

The field of epitranscriptomics encompasses the study of post-transcriptional RNA modifications and their regulatory enzymes. Among the numerous RNA modifications, N⁶-methyladenosine (m⁶A) has been identified as the most common internal modification of messenger RNA (mRNA). Although m⁶A modifications were first discovered in the 1970s, advances in technology have revived interest in this field, driving an abundance of research into the role of RNA modifications in various biological processes, including cancer. As analogs to epigenetic modifications, RNA modifications also play an important role in carcinogenesis by regulating gene expression post-transcriptionally. A growing body of evidence suggests that carcinogens can modulate RNA modifications to alter the expression of oncogenes or tumor suppressors during cellular transformation. Additionally, the expression and activity of the enzymes that regulate RNA modifications can be dysregulated and contribute to carcinogenesis, making these enzymes promising targets of drug discovery. Here we summarize the roles of RNA modifications during carcinogenesis induced by exposure to various environmental carcinogens, with a main focus on the roles of the most widely studied m⁶A mRNA methylation.