Journal
ONCOGENE
Volume 37, Issue 29, Pages 3937-3952Publisher
SPRINGERNATURE
DOI: 10.1038/s41388-018-0223-2
Keywords
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Funding
- Natural Science Foundation of China [81301688, 81572965, 81572689]
- Innovation-Driven Project of Central South University [2017CX012]
- 125 Talent Project of the Third Xiangya Hospital of Central South University
- New Xiangya Talent Project of the Third Xiangya Hospital of Central South University
- New Xiangya Talent Projects of the Third Xiangya Hospital of Central South University [JY201615]
- Scientific Projects of Health and Family Planning Commision of Hunan Province [B2017034]
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Sperm-associated antigen 5 (SPAG5) is involved in various biological processes. However, the roles of SPAG5 in bladder urothelial carcinoma (BUC) are unknown. This study showed that upregulation of SPAG5 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 SPAG5 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, SPAG5 increased the resistance of BUC cells to chemotherapy-induced apoptosis. Mechanistic investigations showed that SPAG5 promotes proliferation and suppresses apoptosis in BUC at least partially via upregulating Wnt3 through activating the AKT/mTOR signaling pathway. The importance of the SPAG5/AKT-mTOR/Wnt3 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 SPAG5 expression is associated with poor survival. In addition, targeting SPAG5 might represent a novel therapeutic strategy to improve the survival of patients with BUC.
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