Research Papers:

Jarid2 is essential for the maintenance of tumor initiating cells in bladder cancer

Xin-Xing Zhu, Ya-Wei Yan, Chun-Zhi Ai, Shan Jiang, Shan-Shan Xu, Min Niu, Xiang-Zhen Wang, Gen-Shen Zhong, Xi-Feng Lu, Yu Xue, Shaoqi Tian, Guangyao Li, Shaojun Tang and Yi-Zhou Jiang _

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Oncotarget. 2017; 8:24483-24490. https://doi.org/10.18632/oncotarget.15522

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Xin-Xing Zhu1,2,*, Ya-Wei Yan1,2,*, Chun-Zhi Ai1, Shan Jiang1, Shan-Shan Xu1, Min Niu3, Xiang-Zhen Wang4, Gen-Shen Zhong5, Xi-Feng Lu6, Yu Xue7, Shaoqi Tian8, Guangyao Li9, Shaojun Tang10, Yi-Zhou Jiang1

1Institute for Advanced Study, Shenzhen University, Shenzhen, Guangdong, China

2Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong, China

3Department of Statics, University of Wisconsin-Madison, Madison, WI, USA

4Maternal and Child Health Hospital of Nanshan District, Shenzhen, Guangdong, China

5The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, China

6Department of Physiology, Center for Diabetes, Obesity and Metabolism, Shenzhen University, Shenzhen, Guangdong, China

7Minnan Normal University, Zhangzhou, Fujian, China

8The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China

9Department of Health Outcomes and Policy, College of Medicine, University of Florida, Gainesville, FL, USA

10Innovation Center for Biomedical Informatics, Georgetown University Medical Center, Washington, DC, USA

*These authors contributed equally to this work

Correspondence to:

Yi-Zhou Jiang, email: [email protected]

Keywords: Jarid2, bladder tumors, tumor-initiating cells, p16, histone modification

Received: November 24, 2016     Accepted: February 07, 2017     Published: February 20, 2017


Bladder cancer is the most common urologic malignancy in China, with an increase of the incidence and mortality rates over past decades. Recent studies suggest that bladder tumors are maintained by a rare fraction of cells with stem cell proprieties. Targeting these bladder tumor initiating cell (TICs) population can overcome the drug-resistance of bladder cancer. However, the molecular and genetic mechanisms regulating TICs in bladder cancer remain poorly defined. Jarid2 is implicated in signaling pathways regulating cancer cell epithelial-mesenchymal transition, and stem cell maintenance. The goal of our study was to examine whether Jarid2 plays a role in the regulation of TICs in bladder cancer. We found that knockdown of Jarid2 was able to inhibit the invasive ability and sphere-forming capacity in bladder cancer cells. Moreover, knockdown of Jarid2 reduced the proportion of TICs and impaired the tumorigenicity of bladder cancer TICs in vivo. Conversely, ectopic overexpression of Jarid2 promoted the invasive ability and sphere-forming capacity in bladder cancer cells. Mechanistically, reduced Jarid2 expression led to the upregulation of p16 and H3K27me3 level at p16 promoter region. Collectively, we provided evidence that Jarid2 via modulation of p16 is a putative novel therapeutic target for treating malignant bladder cancer.

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