RNA methyltransferase NSUN2-mediated m5C methylation promotes Cr(VI)-induced malignant transformation and lung cancer by accelerating metabolism reprogramming
Hexavalent chromium [Cr(VI)], one common environmental contaminant, has long been recognized as a carcinogen associated with lung cancer, but roles and mechanisms of Cr(VI)-induced epigenetic dysregulations in carcinogenesis remain to be investigated. In this study, we identified that RNA m5C methyl...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-10-01
|
| Series: | Environment International |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S016041202400641X |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850210432237699072 |
|---|---|
| author | Rui-Ke Zhang Yan Li Fan-Li Sun Zhi-Hao Zhou Yun-Xia Xie Wen-Jing Liu Wei Wang Jian-Ge Qiu Bing-Hua Jiang Lin Wang |
| author_facet | Rui-Ke Zhang Yan Li Fan-Li Sun Zhi-Hao Zhou Yun-Xia Xie Wen-Jing Liu Wei Wang Jian-Ge Qiu Bing-Hua Jiang Lin Wang |
| author_sort | Rui-Ke Zhang |
| collection | DOAJ |
| description | Hexavalent chromium [Cr(VI)], one common environmental contaminant, has long been recognized as a carcinogen associated with lung cancer, but roles and mechanisms of Cr(VI)-induced epigenetic dysregulations in carcinogenesis remain to be investigated. In this study, we identified that RNA m5C methyltransferase NSUN2 was significantly upregulated in Cr(VI)-transformed cells and lung tissues of Cr(VI)-exposed mice. Inhibition of NSUN2 reduced cell proliferation, migration, colony formation and tube formation abilities. We found NSUN2-mediated m5C modification induced metabolic reprogramming and cell cycle by promoting the mRNA stabilities of ME1, GLUT3 and CDK2. In addition, knockdown of NSUN2 attenuated tumorigenesis and angiogenesis in vivo. RNA m5C reader ALYREF was identified to be involved in NSUN2-mediated m5C modification in Cr (VI)-induced carcinogenesis. Further study showed that EP300 induced NSUN2 upregulation through transcriptional activation by inducing histone modification at H3K27ac site for regulating Cr(VI) carcinogenesis. Our findings demonstrated novel role and mechanism of NSUN2 and epigenetic changes by increasing the RNA m5C modification that are important for Cr (VI)-induced carcinogenesis through NSUN2/ALYREF pathway. NSUN2, ALYREF, ME1, GLUT3 or/and CDK2 may be used as potential new biomarkers or/and therapeutic target(s) in the future. |
| format | Article |
| id | doaj-art-017ba71f7b6e43db87aee787ad35cf7e |
| institution | OA Journals |
| issn | 0160-4120 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj-art-017ba71f7b6e43db87aee787ad35cf7e2025-08-20T02:09:47ZengElsevierEnvironment International0160-41202024-10-0119210905510.1016/j.envint.2024.109055RNA methyltransferase NSUN2-mediated m5C methylation promotes Cr(VI)-induced malignant transformation and lung cancer by accelerating metabolism reprogrammingRui-Ke Zhang0Yan Li1Fan-Li Sun2Zhi-Hao Zhou3Yun-Xia Xie4Wen-Jing Liu5Wei Wang6Jian-Ge Qiu7Bing-Hua Jiang8Lin Wang9Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou 450000, ChinaTianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou 450000, ChinaTianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou 450000, ChinaTianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou 450000, ChinaTianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou 450000, ChinaThe Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450000, ChinaTianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou 450000, ChinaTianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou 450000, ChinaTianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou 450000, China; Corresponding authors.Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou 450000, China; Corresponding authors.Hexavalent chromium [Cr(VI)], one common environmental contaminant, has long been recognized as a carcinogen associated with lung cancer, but roles and mechanisms of Cr(VI)-induced epigenetic dysregulations in carcinogenesis remain to be investigated. In this study, we identified that RNA m5C methyltransferase NSUN2 was significantly upregulated in Cr(VI)-transformed cells and lung tissues of Cr(VI)-exposed mice. Inhibition of NSUN2 reduced cell proliferation, migration, colony formation and tube formation abilities. We found NSUN2-mediated m5C modification induced metabolic reprogramming and cell cycle by promoting the mRNA stabilities of ME1, GLUT3 and CDK2. In addition, knockdown of NSUN2 attenuated tumorigenesis and angiogenesis in vivo. RNA m5C reader ALYREF was identified to be involved in NSUN2-mediated m5C modification in Cr (VI)-induced carcinogenesis. Further study showed that EP300 induced NSUN2 upregulation through transcriptional activation by inducing histone modification at H3K27ac site for regulating Cr(VI) carcinogenesis. Our findings demonstrated novel role and mechanism of NSUN2 and epigenetic changes by increasing the RNA m5C modification that are important for Cr (VI)-induced carcinogenesis through NSUN2/ALYREF pathway. NSUN2, ALYREF, ME1, GLUT3 or/and CDK2 may be used as potential new biomarkers or/and therapeutic target(s) in the future.http://www.sciencedirect.com/science/article/pii/S016041202400641XHexavalent chromiumNSUN2Cell malignant transformationMetabolic reprogrammingTumor growth |
| spellingShingle | Rui-Ke Zhang Yan Li Fan-Li Sun Zhi-Hao Zhou Yun-Xia Xie Wen-Jing Liu Wei Wang Jian-Ge Qiu Bing-Hua Jiang Lin Wang RNA methyltransferase NSUN2-mediated m5C methylation promotes Cr(VI)-induced malignant transformation and lung cancer by accelerating metabolism reprogramming Environment International Hexavalent chromium NSUN2 Cell malignant transformation Metabolic reprogramming Tumor growth |
| title | RNA methyltransferase NSUN2-mediated m5C methylation promotes Cr(VI)-induced malignant transformation and lung cancer by accelerating metabolism reprogramming |
| title_full | RNA methyltransferase NSUN2-mediated m5C methylation promotes Cr(VI)-induced malignant transformation and lung cancer by accelerating metabolism reprogramming |
| title_fullStr | RNA methyltransferase NSUN2-mediated m5C methylation promotes Cr(VI)-induced malignant transformation and lung cancer by accelerating metabolism reprogramming |
| title_full_unstemmed | RNA methyltransferase NSUN2-mediated m5C methylation promotes Cr(VI)-induced malignant transformation and lung cancer by accelerating metabolism reprogramming |
| title_short | RNA methyltransferase NSUN2-mediated m5C methylation promotes Cr(VI)-induced malignant transformation and lung cancer by accelerating metabolism reprogramming |
| title_sort | rna methyltransferase nsun2 mediated m5c methylation promotes cr vi induced malignant transformation and lung cancer by accelerating metabolism reprogramming |
| topic | Hexavalent chromium NSUN2 Cell malignant transformation Metabolic reprogramming Tumor growth |
| url | http://www.sciencedirect.com/science/article/pii/S016041202400641X |
| work_keys_str_mv | AT ruikezhang rnamethyltransferasensun2mediatedm5cmethylationpromotescrviinducedmalignanttransformationandlungcancerbyacceleratingmetabolismreprogramming AT yanli rnamethyltransferasensun2mediatedm5cmethylationpromotescrviinducedmalignanttransformationandlungcancerbyacceleratingmetabolismreprogramming AT fanlisun rnamethyltransferasensun2mediatedm5cmethylationpromotescrviinducedmalignanttransformationandlungcancerbyacceleratingmetabolismreprogramming AT zhihaozhou rnamethyltransferasensun2mediatedm5cmethylationpromotescrviinducedmalignanttransformationandlungcancerbyacceleratingmetabolismreprogramming AT yunxiaxie rnamethyltransferasensun2mediatedm5cmethylationpromotescrviinducedmalignanttransformationandlungcancerbyacceleratingmetabolismreprogramming AT wenjingliu rnamethyltransferasensun2mediatedm5cmethylationpromotescrviinducedmalignanttransformationandlungcancerbyacceleratingmetabolismreprogramming AT weiwang rnamethyltransferasensun2mediatedm5cmethylationpromotescrviinducedmalignanttransformationandlungcancerbyacceleratingmetabolismreprogramming AT jiangeqiu rnamethyltransferasensun2mediatedm5cmethylationpromotescrviinducedmalignanttransformationandlungcancerbyacceleratingmetabolismreprogramming AT binghuajiang rnamethyltransferasensun2mediatedm5cmethylationpromotescrviinducedmalignanttransformationandlungcancerbyacceleratingmetabolismreprogramming AT linwang rnamethyltransferasensun2mediatedm5cmethylationpromotescrviinducedmalignanttransformationandlungcancerbyacceleratingmetabolismreprogramming |