Department of Medicine, Section of Dermatology, University of Chicago, Chicago, Illinois, USA.
Pritzker School of Medicine, University of Chicago, Chicago, Illinois, USA.
Mol Carcinog. 2023 Jan;62(1):24-37. doi: 10.1002/mc.23418. Epub 2022 May 13.
The field of epitranscriptomics encompasses the study of post-transcriptional RNA modifications and their regulatory enzymes. Among the numerous RNA modifications, N -methyladenosine (m A) has been identified as the most common internal modification of messenger RNA (mRNA). Although m A 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 m A mRNA methylation.
表观转录组学领域涵盖了对转录后 RNA 修饰及其调控酶的研究。在众多的 RNA 修饰中，N6-甲基腺苷（m6A）已被确定为信使 RNA（mRNA）中最常见的内部修饰。尽管 m6A 修饰最早在 20 世纪 70 年代被发现，但技术的进步重新激发了人们对这一领域的兴趣，推动了大量关于 RNA 修饰在包括癌症在内的各种生物学过程中的作用的研究。与表观遗传修饰类似，RNA 修饰通过转录后调控基因表达，在致癌作用中也发挥着重要作用。越来越多的证据表明，致癌物质可以调节 RNA 修饰，在细胞转化过程中改变癌基因或肿瘤抑制基因的表达。此外，调节 RNA 修饰的酶的表达和活性也可能失调，并有助于致癌作用，使这些酶成为药物发现的有前途的靶点。在这里，我们总结了暴露于各种环境致癌剂引起的致癌过程中 RNA 修饰的作用，主要集中在研究最广泛的 m6A mRNA 甲基化修饰上。
