2. Academic Validation
  3. Calcitriol induces cell senescence of kidney cancer through JMJD3 mediated histone demethylation

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

  • Oncotarget. 2017 Oct 26;8(59):100187-100195. doi: 10.18632/oncotarget.22124.
Yongqing Shen 1,  Dan Yu 2,  Pan Qi 3,  Xuliang Wang 4,  Xiaoqiang Guo 5 6,  Aili Zhang 3
Affiliations

Affiliations

  • 1 Department of Nursing, Hebei University of Chinese Medicine, Shijiazhuang 050020, Hebei, China.
  • 2 Longgang District Central Hospital, Shenzhen 518116, Guangdong, China.
  • 3 Department of Urology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050035, Hebei, China.
  • 4 Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China.
  • 5 State 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.
  • 6 Department of Urology, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, Guangdong, China.
PMID: 29245970 DOI: 10.18632/oncotarget.22124
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.

Keywords

JMJD3; calcitriol; cell senescence; kidney cancer; p16INK4A.

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