Annexin A8 regulated by lncRNA-TUG1/miR-140-3p axis promotes bladder cancer progression and metastasis

Bladder cancer is the ninth most diagnosed cancer in the world. This study aims to investigate the role and mechanisms of the taurine-upregulated gene 1 (TUG1)/miR-140-3p/annexin A8 (ANXA8) axis in bladder cancer. Western blotting and qRT-PCR determined the expression levels of ANXA8, miR-140-3p, TUG1, and epithelial-mesenchymal transition (EMT) markers. RNA immunoprecipitation (RIP), luciferase assay, and RNA pull-down assay validated the association among ANXA8, miR-140-3p, and TUG1. The biological functions were determined by colony formation, Annexin V-fluorescein isothiocyanate (FITC)/propidium (PI) staining, and transwell assays. Xenograft tumorigenesis detected tumor growth and metastasis in vivo. Pathological analysis was examined by hematoxylin and eosin (H&E) and immunohistochemistry (IHC) analyses. ANXA8 was elevated in bladder tumors and cells. Knockdown of ANXA8 suppressed cell growth, migration, invasion, and EMT in UMUC-3 and T24 cells. ANXA8 was determined as a miR-140-3p target gene. Overexpression of miR-140-3p suppressed cell proliferation, migration, invasion, and EMT via targeting ANXA8. TUG1 promoted ANXA8 expression via sponging miR-140-3p. Silencing of miR-140-3p or ANXA8 overexpression abrogated the tumor-suppressive effects of TUG1 silencing on bladder cancer cell growth and metastasis. The TUG1/miR-140-3p/ANXA8 axis was also implicated in tumor growth and lung metastasis in vivo. TUG1 promotes bladder cancer progression and metastasis through activating ANXA8 by sponging miR-140-3p, which sheds light on the mechanisms of bladder cancer pathogenesis.