The enhanced genomic 6 mA metabolism contributes to the proliferation and migration of TSCC cells.
10.1038/s41368-022-00161-9
- Author:
Lei XI
1
;
Ying YANG
2
;
Ying XU
1
;
Fangming ZHANG
3
;
Jinghui LI
3
;
Xiyang LIU
1
;
Zhenxi ZHANG
1
;
Quan DU
4
Author Information
1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
2. Department of Stomatology, Beijing Friendship Hospital, Capital Medical University, Beijing, China. yangying@ccmu.edu.cn.
3. Department of Stomatology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
4. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China. quan.du@pku.edu.cn.
- Publication Type:Research Support, Non-U.S. Gov't
- MeSH:
AlkB Homolog 1, Histone H2a Dioxygenase/metabolism*;
Carcinoma, Squamous Cell/pathology*;
Cell Line, Tumor;
Cell Movement/genetics*;
Cell Proliferation;
Gene Expression Regulation, Neoplastic;
Humans;
Site-Specific DNA-Methyltransferase (Adenine-Specific)/metabolism*;
Tongue Neoplasms/metabolism*
- From:
International Journal of Oral Science
2022;14(1):11-11
- CountryChina
- Language:English
-
Abstract:
In contrast to the well-established genomic 5-methylcytosine (5mC), the existence of N6-methyladenine (6 mA) in eukaryotic genomes was discovered only recently. Initial studies found that it was actively regulated in cancer cells, suggesting its involvement in the process of carcinogenesis. However, the contribution of 6 mA in tongue squamous cell carcinoma (TSCC) still remains uncharacterized. In this study, a pan-cancer type analysis was first performed, which revealed enhanced 6 mA metabolism in diverse cancer types. The study was then focused on the regulation of 6 mA metabolism, as well as its effects on TSCC cells. To these aspects, genome 6 mA level was found greatly increased in TSCC tissues and cultured cells. By knocking down 6 mA methylases N6AMT1 and METTL4, the level of genomic 6 mA was decreased in TSCC cells. This led to suppressed colony formation and cell migration. By contrast, knockdown of 6 mA demethylase ALKBH1 resulted in an increased 6 mA level, enhanced colony formation, and cell migration. Further study suggested that regulation of the NF-κB pathway might contribute to the enhanced migration of TSCC cells. Therefore, in the case of TSCC, we have shown that genomic 6 mA modification is involved in the proliferation and migration of cancer cells.
