ATP13A2 promoted cell stemness, cisplatin resistance, autophagy, and cell progression of bladder cancer.

BACKGROUND

ATP13A2 is highly expressed in bladder cancer, but its molecular mechanism remains unclear. This study aims to explore whether ATP13A2 regulates cell stemness, autophagy, cisplatin resistance, and progression in bladder cancer.

MATERIALS AND

METHODS

Mouse models and T24 bladder cancer cells were employed. Cells were transfected with ATP13A2-overexpressing vectors or short hairpin RNA (shRNA) targeting ATP13A2 using the Lipofectamine 2000 kit. Tissue morphology was observed by HE staining. ATP13A2 expression was determined by real-time quantitative PCR, western blotting and immunohistochemical (IHC) staining. IHC and immunofluorescence staining were performed to measure LC3 and p62 levels. Cell stemness was assessed using a sphere formation assay. Colony formation, cell counting kit-8 assay, Transwell assays, wound healing test, and flow cytometry were used to evaluate cell proliferation, migration, invasion, and apoptosis. Molecular docking was performed to analyze the interaction between ATP13A2 and the autophagy inhibitor, bafilomycin A1.

RESULTS

ATP13A2 was upregulated in bladder cancer and associated with poor prognosis. Silencing ATP13A2 inhibited cell stemness, cisplatin resistance, and autophagy. Knockdown of ATP13A2 also suppressed cell proliferation, migration, and invasion, while promoting cell apoptosis. Overexpression of ATP13A2 promoted cell stemness, cisplatin resistance, and autophagy. Bafilomycin A1 significantly inhibited cell stemness and reduced drug resistance, suppressing bladder cancer cell progression.

CONCLUSION

Elevated expression of ATP13A2 promotes cell stemness, cisplatin resistance, autophagy, and cell progression in bladder cancer.