Oncotarget

Research Papers:

Calcitriol induces cell senescence of kidney cancer through JMJD3 mediated histone demethylation

Yongqing Shen, Dan Yu, Pan Qi, Xuliang Wang, Xiaoqiang Guo and Aili Zhang _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2017; 8:100187-100195. https://doi.org/10.18632/oncotarget.22124

Metrics: PDF 1415 views  |   HTML 2412 views  |   ?  


Abstract

Yongqing Shen2,*, Dan Yu6,*, Pan Qi1, Xuliang Wang5, Xiaoqiang Guo3,4 and Aili Zhang1

1Department of Urology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050035, Hebei, China

2Department of Nursing, Hebei University of Chinese Medicine, Shijiazhuang 050020, Hebei, China

3State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518035, Guangdong, China

4Department of Urology, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, Guangdong, China

5Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China

6Longgang District Central Hospital, Shenzhen 518116, Guangdong, China

*These authors have contributed equally to this work

Correspondence to:

Aili Zhang, email: [email protected]

Xiaoqiang Guo, email: [email protected]

Keywords: kidney cancer; calcitriol; cell senescence; JMJD3; p16INK4A

Abbreviations: 1,25(OH)2VD3: 1,25-dihydroxyvitamin D3; JMJD3: Jumonji domain-containing protein 3; VDR: vitamin D receptor

Received: July 03, 2017     Accepted: September 29, 2017     Published: October 26, 2017

ABSTRACT

Calcitriol, also known as 1,25-dihydroxyvitamin D3 (1,25(OH)2VD3), is a biologically active form of vitamin D and has a wide range of anticancer activity against various cancer cell lines. However, the mechanism of calcitriol remains to be further studied. In this study, the biological effect and epigenetic regulation of calcitriol on kidney cancer cells were investigated. Calcitriol can significantly inhibit cell proliferation of kidney cancer cell lines 786-O (P<0.05). Calcitriol also induced cell apoptosis and senescence of 786-O and ACHN (P<0.05). Calcitriol can increase the expression of histone demethylase JMJD3 and cell senescence marker p16INK4A (P<0.05). Knockdown of JMJD3 decreased p16INK4A upregulation after calcitriol treatment (P<0.05), and also reduced calcitriol-induced cell senescence (P<0.05). This study reveals a new mechanism of anticancer activity of calcitriol by showing that histone demethylase JMJD3 induced by calcitriol increases p16INK4A expression and cell senescence. Therefore, these results provide new strategy for treatment and prevention of kidney cancer.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 22124