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

Abstract

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.