Evidence map›Paper›PMID 42295564›Full record

ArticleClinical and experimental medicine2026

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

Zhangjie Yang, Jinhu Ma, Ziyang Qiang, Wenhao Xie, Liang Jiao, Zhenxing Hu, Tiange Zhang, Limei Zhang, Jinqiong Lv, Fangqian Yue and 1 more

Abstract read
In one paragraph

Article in Clinical and experimental medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Zhangjie YangClinic Medical school of Qinghai University, Xining, 810000, China.
Jinhu MaClinic Medical school of Qinghai University, Xining, 810000, China.
Ziyang QiangClinic Medical school of Qinghai University, Xining, 810000, China.
Wenhao XieClinic Medical school of Qinghai University, Xining, 810000, China.
Liang JiaoClinic Medical school of Qinghai University, Xining, 810000, China.
Zhenxing HuClinic Medical school of Ningxia medical University, Yinchuan, 750002, China.
Tiange ZhangDepartment of urology, The first affiliated hospital of Southern University of Science and Technology, Shenzhen people's hospital, Shenzhen, 518000, China.
Limei ZhangDepartment of surgery, Shenzhen baoan airsea hospital, Shenzhen, 518000, China.
Jinqiong LvDepartment of general practice, Yongjia second people's hospital, Wenzhou, 325000, China.
Fangqian YueDepartment of surgery, The affiliated Foshan women and children hospital of Guangdong medical University, Foshan, 528000, China.
Guojun ChenDepartment of urology, affiliated hospital of Qinghai University, Xining, 810000, China. chenguojun68@126.com.

Funding

Qinghai Key Construction Project of Specialized Departments of Qinghai University Affiliated Hospital Qinghai Weijianwei [2023]133
6 · The paper itself

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.

Indexed as

AlkB Homolog 2, Alpha-Ketoglutarate-Dependent DioxygenasePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSignal TransductionUrinary Bladder NeoplasmsWarburg Effect, OncologicAnimalsCell Line, TumorCell ProliferationDisease Models, AnimalDisease ProgressionFemaleHumansMaleMetabolic ReprogrammingMiceALKBH2 protein, humanAlkB Homolog 2, Alpha-Ketoglutarate-Dependent DioxygenasePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktALKBH2Bladder cancerHypoxiaPI3K/AKT pathwayWarburg effect

Identifiers

PMID42295564
PMCPMC13500419

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.