Regulations of m⁶A and other RNA modifications and their roles in cancer

Abstract

RNA modification is an essential component of the epitranscriptome, regulating RNA metabolism and cellular functions. Several types of RNA modifications have been identified to date; they include N⁶-methyladenosine (m⁶A), N¹-methyladenosine (m¹A), 5-methylcytosine (m⁵C), N⁷-methylguanosine (m⁷G), N⁶,2′-O-dimethyladenosine (m⁶A_m), N⁴-acetylcytidine (ac⁴C), etc. RNA modifications, mediated by regulators including writers, erasers, and readers, are associated with carcinogenesis, tumor microenvironment, metabolic reprogramming, immunosuppression, immunotherapy, chemotherapy, etc. A novel perspective indicates that regulatory subunits and post-translational modifications (PTMs) are involved in the regulation of writer, eraser, and reader functions in mediating RNA modifications, tumorigenesis, and anticancer therapy. In this review, we summarize the advances made in the knowledge of different RNA modifications (especially m⁶A) and focus on RNA modification regulators with functions modulated by a series of factors in cancer, including regulatory subunits (proteins, noncoding RNA or peptides encoded by long noncoding RNA) and PTMs (acetylation, SUMOylation, lactylation, phosphorylation, etc.). We also delineate the relationship between RNA modification regulator functions and carcinogenesis or cancer progression. Additionally, inhibitors that target RNA modification regulators for anticancer therapy and their synergistic effect combined with immunotherapy or chemotherapy are discussed.

Keywords

RNA modification / writers / erasers / readers / regulatory subunits / PTMs / cancer

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Acknowledgements

This work was supported by National Natural Science Foundation of China (Nos. 82125029, 82073106, and 82341016), Science and Technology Projects in Guangzhou (Nos. 2023A03J0390, 202201020101, and 202201020124).

Compliance with ethics guidelines

Conflicts of interest Xin-Hui Chen, Kun-Xiong Guo, Jing Li, Shu-Hui Xu, Huifang Zhu, and Guang-Rong Yan declare no conflict of interest.

This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

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