A new target: AlkBH2 promotes bladder cancer by upregulation of inflammation

Background : A close relationship exists between inflammation and cancer. Recent studies have highlighted inflammation as a significant contributor to the progression of bladder cancer. However, the role of alkyladenine DNA glycosylase homolog 2 (ALKBH2), an enzyme involved in DNA repair and a member of the ALKB family, in the context of bladder cancer inflammation remains largely unexplored. Methods : We evaluated ALKBH2 expression in bladder cancer tissues and adjacent normal tissues using hematoxylin and eosin (H&E) staining and immunohistochemistry. The clinical significance of ALKBH2 expression was further assessed through quantitative real-time polymerase chain reaction (Q-PCR) and Western blotting. To explore the functional implications of ALKBH2, we generated stable cell lines with overexpression and knockdown of ALKBH2. Functional assays, including Cell Counting Kit-8 (CCK-8), colony formation, Transwell migration and invasion, and wound healing assays, were conducted to assess the impact of ALKBH2 on cell proliferation, migration, and invasion. Additionally, the influence of ALKBH2 on inflammation in bladder cancer cells was investigated. Results : Our findings demonstrate that ALKBH2 promotes the proliferation, colony formation, migration, and invasion of bladder cancer cells. Mechanistically, ALKBH2 activates the nuclear factor-kappa B (NF-κB) signaling pathway, which in turn drives the progression of bladder cancer. Conclusion : These results suggest that ALKBH2 plays a critical oncogenic role in bladder cancer by modulating inflammation through the activation of the NF-κB pathway and the suppression of the NRF2/HO-1 signaling pathway. These findings highlight the potential of ALKBH2 as a therapeutic target for bladder cancer treatment.