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BioMed Research International
Volume 2017, Article ID 3781904, 14 pages
Research Article

Knockdown of SIRT1 Suppresses Bladder Cancer Cell Proliferation and Migration and Induces Cell Cycle Arrest and Antioxidant Response through FOXO3a-Mediated Pathways

1Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
2Department of Endocrinology, The First Affiliated Hospital of Zhejiang University, Hangzhou, China
3Medical Research Institute, Wuhan University, Wuhan, China
4Center for Medical Science Research, Zhongnan Hospital of Wuhan University, Wuhan, China
5Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
6Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China

Correspondence should be addressed to Yu Xiao; and Xinghuan Wang; nc.ude.uhw@nauhgnixgnaw

Received 4 May 2017; Accepted 7 August 2017; Published 25 September 2017

Academic Editor: Antoni Camins

Copyright © 2017 Qingxuan Hu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Bladder cancer (BCa) is one of the most common tumors, but its underlying mechanism has not been fully clarified. Our transcriptome analysis suggested a close link of Sirtuins, Peroxisome Proliferator-Activated Receptor (PPAR), cell cycle regulation, reactive oxygen species (ROS) metabolism, and Forkhead Box Class O (FOXO) signaling pathway in BCa. SIRT1 is a key member of Sirtuins, playing important roles in aging and energy metabolism, which has been reported to be involved in various metabolic diseases and tumors. We observed that SIRT1 was upregulated in BCa tissues at both mRNA and protein levels. By establishing a SIRT1-knockdown BCa cell model, our results suggested that proliferation and viability were suppressed. Moreover, migration rate was inhibited as well, possibly via reduction of epithelial-mesenchymal transition (EMT). In addition, cell cycle arrest was significantly induced, consisting with strongly decreased proteins involved (CDK2/4/6). Furthermore, ROS production was slightly reduced, accompanied by increasing of antioxidant enzymes and total/acetylated FOXO3a. Consistently with our Path-net analysis, we observed no significant alteration of apoptosis in the SIRT1-knockdown BCa cells. Taken together, our results suggested that SIRT1 deficiency in BCa cells could suppress cell viability by activating antioxidant response and inducing cell cycle arrest possibly via FOXO3a-related pathways.