Long noncoding RNA DANCR promotes invasion of prostate cancer through epigenetically silencing expression of TIMP2/3
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Jing Jia1, Feng Li1, Xiao-Shuang Tang1, Shan Xu1,2, Yang Gao1, Qi Shi1, Wenhuan Guo3, Xinyang Wang1,2, Dalin He1,2, Peng Guo1,2
1Department of Urology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
2Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an, Shaanxi, China
3Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
Peng Guo, email: [email protected]
Dalin He, email: [email protected]
Keywords: DANCR, prostate cancer, TIMP2, TIMP3, EZH2
Received: November 01, 2015 Accepted: May 01, 2016 Published: May 13, 2016
LncRNA DANCR suppresses differentiation of epithelial cells, however, its function in prostate cancer development is still unknown. In the present study, we found the expression of DANCR increases in prostate cancer tissues and cells compared to normal prostate tissues and cells, moreover, DANCR promotes invasion and migration of prostate cancer cells in vitro and metastasis of tumor xenografts in nude mice. Mechanistically, we found that TIMP2/3, which are critical metastasis inhibitor of prostate cancer, were down-regulated by DANCR synergistically with EZH2 through epigenetically silencing their promoter by chromatin immunoprecipitation assay. In addition, we further investigated whether DANCR is regulated by the differentiation-promoting androgen-androgen receptor (AR) pathway and found that DANCR expression is repressed by androgen-AR; furthermore, DANCR impedes the upregulation of TIMP2/3 and the suppression of invasion and migration by androgen-AR. On the other hand, interestingly, we found that in prostate cancer cells DANCR knockdown decreased the promotion of invasion and migration by the treatment of enzalutamide, which is an AR inhibitor. In summary, our results indicate that DANCR promotes prostate cancer invasion and metastasis through repressing the expression of TIMP2/3, and suggest that DANCR could be a potential target for preventing prostate cancer metastasis, and knockdown DANCR may lessen the potential side effect of AR inhibitor.
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