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

• Published in: Molecular therapy. Nucleic acids Vol. 23; pp. 27 - 41
• Main Authors: Yu, Hao, Yang, Xiao, Tang, Jinyuan, Si, Shuhui, Zhou, Zijian, Lu, Jiancheng, Han, Jie, Yuan, Baorui, Wu, Qikai, Lu, Qiang, Yang, Haiwei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.03.2021; American Society of Gene & Cell Therapy; Elsevier
• Subjects: ALKBH5; bladder cancer; cisplatin; glycolysis; m6A; Original; protein kinase CK2α; m6A; ALKBH5; protein kinase CK2α; cisplatin; bladder cancer; glycolysis
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1016/j.omtn.2020.10.031

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. [Display omitted] Yu et al. show that m6A demethylase ALKBH5 was correlated with the prognosis of bladder cancer patients, inhibited bladder cancer cell proliferation, and sensitized bladder cancer cells to cisplatin in vitro and in vivo by CK2α-mediated glycolysis in an m6A-dependent manner, which might provide fresh insights into bladder cancer therapy.