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 () and Ming-Jer Tsai ()
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Shih-Chieh Lin: Baylor College of Medicine
Chung-Yang Kao: Baylor College of Medicine
Hui-Ju Lee: Baylor College of Medicine
Chad J. Creighton: Baylor College of Medicine
Michael M. Ittmann: Baylor College of Medicine
Shaw-Jenq Tsai: College of Medicine, National Cheng Kung University
Sophia Y. Tsai: Baylor College of Medicine
Ming-Jer Tsai: Baylor College of Medicine

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/ncomms11418

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