ALKBH5 promotes cadmium-induced transformation of human bronchial epithelial cells by regulating PTEN expression in an m6A-dependent manner
Cadmium is a carcinogenic heavy metal that poses a severe threat to human beings. The underlying mechanism, however, remains elusive. N6-methyladenosine (m6A) is the most abundant post-transcriptional modification in mRNA that regulates RNA metabolism. Emerging evidence shows that m6A is involved in...
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doaj-37cdf0c4fcfd48e0b5dc694dcbdb27832021-09-05T04:38:29ZengElsevierEcotoxicology and Environmental Safety0147-65132021-11-01224112686ALKBH5 promotes cadmium-induced transformation of human bronchial epithelial cells by regulating PTEN expression in an m6A-dependent mannerLuyao Li0Mei Zhou1Biyun Chen2Qin Wang3Shuya Pan4Yaxuan Hou5Jiamin Xia6Xue Zhou7Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR ChinaDepartment of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR ChinaDepartment of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR ChinaDepartment of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR ChinaDepartment of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR ChinaDepartment of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR ChinaDepartment of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR ChinaCorrespondence to: Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei 430030, PR China.; Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR ChinaCadmium is a carcinogenic heavy metal that poses a severe threat to human beings. The underlying mechanism, however, remains elusive. N6-methyladenosine (m6A) is the most abundant post-transcriptional modification in mRNA that regulates RNA metabolism. Emerging evidence shows that m6A is involved in the pathogenesis of various cancers. In this study, human bronchial epithelial BEAS-2B cells were transformed by exposing to 2 μM of cadmium for 20 weeks to investigate the role of m6A in cadmium carcinogenesis. We found the level of m6A in mRNA was significantly decreased in cadmium-transformed BEAS-2B cells, and this change was regulated by m6A demethylase ALKBH5. ALKBH5 was significantly upregulated in the middle and late stages of cell transformation at week 8, 12, 16 and 20. Knockdown of ALKBH5 in cadmium-transformed cells alleviated cell proliferation, migration, invasion, and anchorage-independent growth, but co-transfection with ALKBH5 siRNA and PTEN siRNA restored the inhibitory effects of ALKBH5 knockdown on those transformation properties. ALKBH5 decreased the m6A level of PTEN mRNA, resulting in its instability and reduction of PTEN protein expression. These results indicate that ALKBH5-mediated demethylation m6A at PTEN mRNA is involved in cadmium-induced cell transformation. Our study provides a new perspective for the involvement of m6A modification in cadmium carcinogenesis.http://www.sciencedirect.com/science/article/pii/S0147651321007983CadmiumALKBH5M6A modificationPTENCell transformation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Luyao Li Mei Zhou Biyun Chen Qin Wang Shuya Pan Yaxuan Hou Jiamin Xia Xue Zhou |
spellingShingle |
Luyao Li Mei Zhou Biyun Chen Qin Wang Shuya Pan Yaxuan Hou Jiamin Xia Xue Zhou ALKBH5 promotes cadmium-induced transformation of human bronchial epithelial cells by regulating PTEN expression in an m6A-dependent manner Ecotoxicology and Environmental Safety Cadmium ALKBH5 M6A modification PTEN Cell transformation |
author_facet |
Luyao Li Mei Zhou Biyun Chen Qin Wang Shuya Pan Yaxuan Hou Jiamin Xia Xue Zhou |
author_sort |
Luyao Li |
title |
ALKBH5 promotes cadmium-induced transformation of human bronchial epithelial cells by regulating PTEN expression in an m6A-dependent manner |
title_short |
ALKBH5 promotes cadmium-induced transformation of human bronchial epithelial cells by regulating PTEN expression in an m6A-dependent manner |
title_full |
ALKBH5 promotes cadmium-induced transformation of human bronchial epithelial cells by regulating PTEN expression in an m6A-dependent manner |
title_fullStr |
ALKBH5 promotes cadmium-induced transformation of human bronchial epithelial cells by regulating PTEN expression in an m6A-dependent manner |
title_full_unstemmed |
ALKBH5 promotes cadmium-induced transformation of human bronchial epithelial cells by regulating PTEN expression in an m6A-dependent manner |
title_sort |
alkbh5 promotes cadmium-induced transformation of human bronchial epithelial cells by regulating pten expression in an m6a-dependent manner |
publisher |
Elsevier |
series |
Ecotoxicology and Environmental Safety |
issn |
0147-6513 |
publishDate |
2021-11-01 |
description |
Cadmium is a carcinogenic heavy metal that poses a severe threat to human beings. The underlying mechanism, however, remains elusive. N6-methyladenosine (m6A) is the most abundant post-transcriptional modification in mRNA that regulates RNA metabolism. Emerging evidence shows that m6A is involved in the pathogenesis of various cancers. In this study, human bronchial epithelial BEAS-2B cells were transformed by exposing to 2 μM of cadmium for 20 weeks to investigate the role of m6A in cadmium carcinogenesis. We found the level of m6A in mRNA was significantly decreased in cadmium-transformed BEAS-2B cells, and this change was regulated by m6A demethylase ALKBH5. ALKBH5 was significantly upregulated in the middle and late stages of cell transformation at week 8, 12, 16 and 20. Knockdown of ALKBH5 in cadmium-transformed cells alleviated cell proliferation, migration, invasion, and anchorage-independent growth, but co-transfection with ALKBH5 siRNA and PTEN siRNA restored the inhibitory effects of ALKBH5 knockdown on those transformation properties. ALKBH5 decreased the m6A level of PTEN mRNA, resulting in its instability and reduction of PTEN protein expression. These results indicate that ALKBH5-mediated demethylation m6A at PTEN mRNA is involved in cadmium-induced cell transformation. Our study provides a new perspective for the involvement of m6A modification in cadmium carcinogenesis. |
topic |
Cadmium ALKBH5 M6A modification PTEN Cell transformation |
url |
http://www.sciencedirect.com/science/article/pii/S0147651321007983 |
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