Demethylases in tumors and the tumor microenvironment: Key modifiers of N6-methyladenosine methylation

Junchen Guo; Liang Zhao; Meiqi Duan; Zhi Yang; He Zhao; Baiming Liu; Yihan Wang; Liping Deng; Chen Wang; Xiaodi Jiang; Xiaofeng Jiang

doi:10.1016/j.biopha.2024.116479

Demethylases in tumors and the tumor microenvironment: Key modifiers of N⁶-methyladenosine methylation

Biomed Pharmacother. 2024 Mar 26:174:116479. doi: 10.1016/j.biopha.2024.116479. Online ahead of print.

Authors

Junchen Guo¹, Liang Zhao², Meiqi Duan³, Zhi Yang³, He Zhao³, Baiming Liu³, Yihan Wang³, Liping Deng³, Chen Wang³, Xiaodi Jiang⁴, Xiaofeng Jiang⁵

Affiliations

¹ Departmentof Radiology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, China.
² Department of Anorectal Surgery, Shenyang Anorectal Hospital, Shenyang, Liaoning 110002, China.
³ Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, China.
⁴ Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110002, China. Electronic address: lindajiang1983@aliyun.com.
⁵ Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, China. Electronic address: 18900912171@163.com.

PMID: 38537580
DOI: 10.1016/j.biopha.2024.116479

Abstract

RNA methylation modifications are widespread in eukaryotes and prokaryotes, with N⁶-methyladenosine (m⁶A) the most common among them. Demethylases, including Fat mass and obesity associated gene (FTO) and AlkB homolog 5 (ALKBH5), are important in maintaining the balance between RNA methylation and demethylation. Recent studies have clearly shown that demethylases affect the biological functions of tumors by regulating their m⁶A levels. However, their effects are complicated, and even opposite results have appeared in different articles. Here, we summarize the complex regulatory networks of demethylases, including the most important and common pathways, to clarify the role of demethylases in tumors. In addition, we describe the relationships between demethylases and the tumor microenvironment, and introduce their regulatory mechanisms. Finally, we discuss evaluation of demethylases for tumor diagnosis and prognosis, as well as the clinical application of demethylase inhibitors, providing a strong basis for their large-scale clinical application in the future.

Keywords: Cancer; Demethylases; Molecular mechanism; TME; Therapy; m(6)A.

Publication types

Review