ALKBH2 promotes the Warburg effect and bladder cancer progression under hypoxic conditions via the PI3K/AKT pathway.

Authors

Zhangjie Yang, Jinhu Ma, Ziyang Qiang, Wenhao Xie, Liang Jiao, Zhenxing Hu, Tiange Zhang, Limei Zhang, Jinqiong Lv, Fangqian Yue, Guojun Chen

Published in

Clinical and experimental medicine. Jun 15, 2026. Epub Jun 15, 2026.

Abstract

Emerging evidence links DNA repair enzymes to metabolic reprogramming in cancer. ALKBH2 safeguards genomic integrity by reversing alkylation damage, yet its potential role beyond repair-specifically in modulating the Warburg effect-remains unexplored in bladder cancer. While implicated in digestive tract malignancies, ALKBH2's function in urothelial carcinoma is unknown. Investigating this gap may reveal ALKBH2 as a novel metabolic driver in bladder cancer progression. ALKBH2 expression was analyzed in bladder cancer tissues and matched adjacent normal tissues by qPCR, Western blotting, and immunofluorescence (IF). Hematoxylin and eosin (H&E) staining was used to confirm tissue histology. Using stable ALKBH2-overexpressing and knockdown bladder cancer cell lines, we systematically assessed the effects of ALKBH2 on tumor cell behavior in vitro and tumor growth in vivo. Moreover, its involvement in hypoxia-associated Warburg metabolic reprogramming was investigated under 1% O₂. In vitro, ALKBH2 overexpression enhanced bladder cancer cell proliferation, migration, invasion, and clonogenicity, whereas ALKBH2 knockdown exerted opposite effects. Consistently, in vivo xenograft models demonstrated that silencing ALKBH2 significantly suppressed tumor growth. Mechanistic investigations revealed that ALKBH2 functions as an m6A demethylase to reduce PTEN mRNA stability, thereby activates the PI3K/AKT signaling pathway under hypoxic conditions, as evidenced by increased pathway activation, thereby facilitating metabolic reprogramming and tumor cell progression. These findings suggest that ALKBH2 plays a critical oncogenic role in bladder cancer by regulating PI3K/AKT pathway activation and promoting the Warburg effect, highlighting its potential as a therapeutic target for bladder cancer.

PMID:
42295564
Bibliographic data and abstract were imported from PubMed on 15 Jun 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.