Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1783624465602576384 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7744648 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT yuhao alkbh5inhibitedcellproliferationandsensitizedbladdercancercellstocisplatinbym6ack2amediatedglycolysis AT yangxiao alkbh5inhibitedcellproliferationandsensitizedbladdercancercellstocisplatinbym6ack2amediatedglycolysis AT tangjinyuan alkbh5inhibitedcellproliferationandsensitizedbladdercancercellstocisplatinbym6ack2amediatedglycolysis AT sishuhui alkbh5inhibitedcellproliferationandsensitizedbladdercancercellstocisplatinbym6ack2amediatedglycolysis AT zhouzijian alkbh5inhibitedcellproliferationandsensitizedbladdercancercellstocisplatinbym6ack2amediatedglycolysis AT lujiancheng alkbh5inhibitedcellproliferationandsensitizedbladdercancercellstocisplatinbym6ack2amediatedglycolysis AT hanjie alkbh5inhibitedcellproliferationandsensitizedbladdercancercellstocisplatinbym6ack2amediatedglycolysis AT yuanbaorui alkbh5inhibitedcellproliferationandsensitizedbladdercancercellstocisplatinbym6ack2amediatedglycolysis AT wuqikai alkbh5inhibitedcellproliferationandsensitizedbladdercancercellstocisplatinbym6ack2amediatedglycolysis AT luqiang alkbh5inhibitedcellproliferationandsensitizedbladdercancercellstocisplatinbym6ack2amediatedglycolysis AT yanghaiwei alkbh5inhibitedcellproliferationandsensitizedbladdercancercellstocisplatinbym6ack2amediatedglycolysis |