SYT7 Acts as Tumor Promotor in Development of Bladder Cancer Through Targeting POLE2

Abstract

Background: Nowadays, bladder cancer has been recognized as a serious threaten to human health in urological system, the research of molecular mechanism of which may benefit for its treatment. This study aimed to explore the regulatory role and mechanism of SYT7 in the development and progression of bladder cancer. Methods: IHC analysis was performed to detect the expression of SYT7 in clinical specimens. Cell models were constructed based on lentivirus-mediated gene regulation. Evaluation of cell phenotypes including cell proliferation, cell apoptosis and cell migration was used to reveal the role of SYT7 in bladder cancer, which was further verified by mice xenograft model. Moreover, a genechip analysis was performed to explore the downstream mechanism of SYT7 in bladder cancer. Finding: It was indicated that SYT7 was up-regulated in bladder cancer tissues in comparison with normal tissues and significantly associated with more advanced pathological grade. In vitro and in vivo studies showed that knockdown of SYT7 could inhibit bladder cancer development through regulating proliferation, colony formation, apoptosis and migration of bladder cancer cells. Mechanistically, we identified POLE2 as a potential downstream target of SYT7 in bladder cancer cells. Down-regulation of POLE2 also inhibits bladder cancer development in vitro and is capable of alleviating the promotion of bladder cancer induced by SYT7 overexpression. Interpretation: SYT7 and POLE2 were both found to be critical regulator in the development and progression of bladder cancer and SYT7 may execute its functions through POLE2. Funding Statement: This work was financially supported by National Natural Science Foundation of China (No.81402116, No.81772718) and Natural Science Foundation of Guangdong Province, China (No. 2017A030313847). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: Patients were completely informed before the collection of the tissue samples and the experimental design was approved by the Ethics Committee of the First Affiliated Hospital, Sun Yat-Sen University.