AlkBH2 promotes the Warburg effect of bladder cancer via activating the PI3K/AKT signaling pathway

AlkBH2, a major dioxygenase involved in repairing alkylation damage in genomic DNA, particularly within ribosome-DNA genes, has shown potential clinical significance in various human cancers. While its role has been investigated in digestive system tumors like rectal and gastric cancer, the function and underlying mechanisms of AlkBH2 in bladder cancer progression remain largely unknown. We compared AlkBH2 expression in bladder cancer and adjacent normal tissues using HE staining and immunofluorescence. The clinical significance of AlkBH2 expression was assessed by Q-PCR and Western blotting. Stable AlkBH2-overexpressing and knockdown cell lines were generated for functional assays, including CCK-8, colony formation, Transwell migration and invasion, and wound healing assays. In vivo tumor growth was evaluated using a subcutaneous xenograft mouse model. The influence of AlkBH2 on the Warburg effect in bladder cancer cells was investigated under hypoxic conditions. AlkBH2 promoted the proliferation, colony formation, migration, and invasion of bladder cancer cells in vitro. Conversely, knockdown of AlkBH2 suppressed tumor growth both in vivo and in vitro. Mechanistically, under hypoxic conditions, AlkBH2 activated the PI3K/AKT signaling pathway, thereby promoting bladder cancer 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.