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ALKBH5 Inhibited Cell Proliferation and Sensitized Bladder Cancer Cells to Cisplatin by m6A-CK2α-Mediated Glycolysis

N6-methyladenosine (m6A) is the most commonly occurring internal RNA modification to be found in eukaryotic mRNA and serves an important role in various physiological events. AlkB homolog 5 RNA demethylase (ALKBH5), an m6A demethylase, belongs to the AlkB family of dioxygenases and has been shown to...

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Autores principales: Yu, Hao, Yang, Xiao, Tang, Jinyuan, Si, Shuhui, Zhou, Zijian, Lu, Jiancheng, Han, Jie, Yuan, Baorui, Wu, Qikai, Lu, Qiang, Yang, Haiwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744648/
https://www.ncbi.nlm.nih.gov/pubmed/33376625
http://dx.doi.org/10.1016/j.omtn.2020.10.031
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author Yu, Hao
Yang, Xiao
Tang, Jinyuan
Si, Shuhui
Zhou, Zijian
Lu, Jiancheng
Han, Jie
Yuan, Baorui
Wu, Qikai
Lu, Qiang
Yang, Haiwei
author_facet Yu, Hao
Yang, Xiao
Tang, Jinyuan
Si, Shuhui
Zhou, Zijian
Lu, Jiancheng
Han, Jie
Yuan, Baorui
Wu, Qikai
Lu, Qiang
Yang, Haiwei
author_sort Yu, Hao
collection PubMed
description N6-methyladenosine (m6A) is the most commonly occurring internal RNA modification to be found in eukaryotic mRNA and serves an important role in various physiological events. AlkB homolog 5 RNA demethylase (ALKBH5), an m6A demethylase, belongs to the AlkB family of dioxygenases and has been shown to specifically demethylate m6A in RNA, which is associated with a variety of tumors. However, its function in bladder cancer remains largely unclear. In the present study, we found that the expression of ALKBH5 was downregulated in bladder cancer tissues and cell lines. Low expression of ALKBH5 was correlated with the worse prognosis of bladder cancer patients. Furthermore, functional assays revealed that knockdown of ALKBH5 promoted bladder cancer cell proliferation, migration, invasion, and decreased cisplatin chemosensitivity in the 5637 and T24 bladder cancer cell lines in vivo and in vitro, whereas ALKBH5 overexpression led to the opposite results. Finally, ALKBH5 inhibited the progression and sensitized bladder cancer cells to cisplatin through a casein kinase 2 (CK2)α-mediated glycolysis pathway in an m6A-dependent manner. Taken together, these findings might provide fresh insights into bladder cancer therapy.
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spelling pubmed-77446482020-12-28 ALKBH5 Inhibited Cell Proliferation and Sensitized Bladder Cancer Cells to Cisplatin by m6A-CK2α-Mediated Glycolysis Yu, Hao Yang, Xiao Tang, Jinyuan Si, Shuhui Zhou, Zijian Lu, Jiancheng Han, Jie Yuan, Baorui Wu, Qikai Lu, Qiang Yang, Haiwei Mol Ther Nucleic Acids Original Article N6-methyladenosine (m6A) is the most commonly occurring internal RNA modification to be found in eukaryotic mRNA and serves an important role in various physiological events. AlkB homolog 5 RNA demethylase (ALKBH5), an m6A demethylase, belongs to the AlkB family of dioxygenases and has been shown to specifically demethylate m6A in RNA, which is associated with a variety of tumors. However, its function in bladder cancer remains largely unclear. In the present study, we found that the expression of ALKBH5 was downregulated in bladder cancer tissues and cell lines. Low expression of ALKBH5 was correlated with the worse prognosis of bladder cancer patients. Furthermore, functional assays revealed that knockdown of ALKBH5 promoted bladder cancer cell proliferation, migration, invasion, and decreased cisplatin chemosensitivity in the 5637 and T24 bladder cancer cell lines in vivo and in vitro, whereas ALKBH5 overexpression led to the opposite results. Finally, ALKBH5 inhibited the progression and sensitized bladder cancer cells to cisplatin through a casein kinase 2 (CK2)α-mediated glycolysis pathway in an m6A-dependent manner. Taken together, these findings might provide fresh insights into bladder cancer therapy. American Society of Gene & Cell Therapy 2020-10-22 /pmc/articles/PMC7744648/ /pubmed/33376625 http://dx.doi.org/10.1016/j.omtn.2020.10.031 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Yu, Hao
Yang, Xiao
Tang, Jinyuan
Si, Shuhui
Zhou, Zijian
Lu, Jiancheng
Han, Jie
Yuan, Baorui
Wu, Qikai
Lu, Qiang
Yang, Haiwei
ALKBH5 Inhibited Cell Proliferation and Sensitized Bladder Cancer Cells to Cisplatin by m6A-CK2α-Mediated Glycolysis
title ALKBH5 Inhibited Cell Proliferation and Sensitized Bladder Cancer Cells to Cisplatin by m6A-CK2α-Mediated Glycolysis
title_full ALKBH5 Inhibited Cell Proliferation and Sensitized Bladder Cancer Cells to Cisplatin by m6A-CK2α-Mediated Glycolysis
title_fullStr ALKBH5 Inhibited Cell Proliferation and Sensitized Bladder Cancer Cells to Cisplatin by m6A-CK2α-Mediated Glycolysis
title_full_unstemmed ALKBH5 Inhibited Cell Proliferation and Sensitized Bladder Cancer Cells to Cisplatin by m6A-CK2α-Mediated Glycolysis
title_short ALKBH5 Inhibited Cell Proliferation and Sensitized Bladder Cancer Cells to Cisplatin by m6A-CK2α-Mediated Glycolysis
title_sort alkbh5 inhibited cell proliferation and sensitized bladder cancer cells to cisplatin by m6a-ck2α-mediated glycolysis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744648/
https://www.ncbi.nlm.nih.gov/pubmed/33376625
http://dx.doi.org/10.1016/j.omtn.2020.10.031
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