J Cancer 2017; 8(12):2282-2295. doi:10.7150/jca.19967 This issue Cite

Research Paper

Silencing of HJURP induces dysregulation of cell cycle and ROS metabolism in bladder cancer cells via PPARγ-SIRT1 feedback loop

Rui Cao1, Gang Wang1, Kaiyu Qian1,2, Liang Chen1, Guofeng Qian3, Conghua Xie4, Han C. Dan5, Wei Jiang1,6, Min Wu7, Chin-Lee Wu8, Yu Xiao1,9✉, Xinghuan Wang1✉

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.

Citation:
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. https://www.jcancer.org/v08p2282.htm
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Abstract

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


Citation styles

APA
Cao, R., Wang, G., Qian, K., Chen, L., Qian, G., Xie, C., Dan, H.C., Jiang, W., Wu, M., Wu, C.L., Xiao, Y., Wang, X. (2017). Silencing of HJURP induces dysregulation of cell cycle and ROS metabolism in bladder cancer cells via PPARγ-SIRT1 feedback loop. Journal of Cancer, 8(12), 2282-2295. https://doi.org/10.7150/jca.19967.

ACS
Cao, R.; Wang, G.; Qian, K.; Chen, L.; Qian, G.; Xie, C.; Dan, H.C.; Jiang, W.; Wu, M.; Wu, C.L.; 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.

NLM
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. https://www.jcancer.org/v08p2282.htm

CSE
Cao R, Wang G, Qian K, Chen L, Qian G, Xie C, Dan HC, Jiang W, Wu M, Wu CL, Xiao Y, Wang X. 2017. Silencing of HJURP induces dysregulation of cell cycle and ROS metabolism in bladder cancer cells via PPARγ-SIRT1 feedback loop. J Cancer. 8(12):2282-2295.

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