SPAG5 promotes proliferation and suppresses apoptosis in bladder urothelial carcinoma by upregulating Wnt3 via activating the AKT/mTOR pathway and predicts poorer survival.

Sperm-associated antigen 5 is involved in various biological processes. However, the roles of in bladder urothelial carcinoma (BUC) are unknown. This study showed that upregulation of duanyu1842G5 was detected frequently in primary BUC tissues, and was associated with significantly worse survival among the 112 patients that underwent radical cystectomy (RC). Up and downregulating the expression of duanyu1842G5 enhanced or inhibited, respectively, the proliferation of BUC cells in vitro and in vivo, and suppressed or enhanced, respectively, apoptosis in vitro and in vivo. Moreover, duanyu1842G5 increased the resistance of BUC cells to chemotherapy-induced apoptosis. Mechanistic investigations showed that duanyu1842G5 promotes proliferation and suppresses apoptosis in BUC at least partially via upregulating Wnt3 through activating the AKT/mTOR signaling pathway. The importance of the axis identified in BUC cell models was confirmed via immunohistochemical analysis of a cohort of human BUC specimens that underwent RC. Collectively, our data suggested that in patients with BUC who underwent RC, high duanyu1842G5 expression is associated with poor survival. In addition, targeting duanyu1842G5 might represent a novel therapeutic strategy to improve the survival of patients with BUC.

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