J Cancer 2017; 8(12):2282-2295. doi:10.7150/jca.19967
Silencing of HJURP induces dysregulation of cell cycle and ROS metabolism in bladder cancer cells via PPARγ-SIRT1 feedback loop
1. Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China;
2. Department of Urology, The Fifth Hospital of Wuhan, Wuhan, China;
3. Department of Endocrinology, The First Affiliated Hospital of Zhejiang University, Hangzhou, China;
4. Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.
5. Greenebaum Cancer Center, School of Medicine, University of Maryland, Baltimore, MD, USA.
6. Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China;
7. College of Life Science, Wuhan University, Wuhan, China.
8. Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
9. Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China.
Holliday Junction Recognition Protein (HJURP) is a centromeric histone chaperone involving in de novo histone H3 variant CenH3 (CENP-A) recruitment. Our transcriptome and in vivo study revealed that HJURP is significantly upregulated in bladder cancer (BCa) tissues at both mRNA and protein levels. Knockdown of HJURP inhibited proliferation and viability of BCa cell lines revealed by CCK-8, colony formation and Ki-67-staining assays, and induced apoptosis and reactive oxygen species (ROS) production, as well as triggered cell cycle arrest at G0/G1 phase possibly via loss of CENP-A. Interestingly, in the HJURP-reduced BCa cells the levels of PPARγ and acetylated-p53 were increased, while the ratio of phosphorylated/total SIRT1 protein was decreased. Moreover, after treatment of the BCa cells using PPARγ antagonist (GW9662) and SIRT1 agonist (resveratrol, RSV) respectively, thee phenotypes of cell cycle arrest, increased ROS production and inhibited proliferation rate were all rescued. Taken together, our results suggested that HJURP might regulate proliferation and apoptosis via the PPARγ-SIRT1 negative feedback loop in BCa cells.
Keywords: Bladder cancer, HJURP, cell cycle, ROS, PPARγ, SIRT1
Cao R, Wang G, Qian K, Chen L, Qian G, Xie C, Dan HC, Jiang W, Wu M, Wu CL, Xiao Y, Wang X. Silencing of HJURP induces dysregulation of cell cycle and ROS metabolism in bladder cancer cells via PPARγ-SIRT1 feedback loop. J Cancer 2017; 8(12):2282-2295. doi:10.7150/jca.19967. Available from http://www.jcancer.org/v08p2282.htm