Dysregulation of miRNAs-COUP-TFII-FOXM1-CENPF axis contributes to the metastasis of prostate cancer

Shih Chieh Lin, Chung Yang Kao, Hui Ju Lee, Chad J. Creighton, Michael M. Ittmann, Shaw Jenq Tsai, Sophia Y. Tsai, Ming Jer Tsai

研究成果: Article同行評審

53 引文 斯高帕斯(Scopus)

摘要

Although early detection and treatment of prostate cancer (PCa) improves outcomes, many patients still die of metastatic PCa. Here, we report that metastatic PCa exhibits reduced levels of the microRNAsmiR-101 and miR-27a. These micro-RNAs (miRNAs) negatively regulate cell invasion and inhibit the expression of FOXM1 and CENPF, two master regulators of metastasis in PCa. Interestingly, the repression of FOXM1 and CENPF by these miRNAs occurs through COUP-TFII, a member of the orphan nuclear receptors family. Loss of miR-101 positively correlates with the increase of COUP-TFII-FOXM1-CENPF activity in clinical PCa data sets, implicating clinical relevance of such regulation. Further studies show that COUP-TFII is a critical factor controlling metastatic gene networks to promote PCa metastasis. Most importantly, this miRNA-COUP-TFII-FOXM1-CENPF regulatory axis is also involved in the development of enzalutaminde resistance. Taken together, our findings highlight the contribution of specific miRNAs through the regulation of the COUP-TFII-FOXM1-CENPF cascade in PCa metastasis and drug resistance.

原文English
文章編號11418
期刊Nature communications
7
DOIs
出版狀態Published - 2016 四月 25

All Science Journal Classification (ASJC) codes

  • 化學 (全部)
  • 生物化學、遺傳與分子生物學 (全部)
  • 物理與天文學 (全部)

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