Journal Article

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

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

2016

Overview

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. The orphan nuclear receptor COUP-TFII is highly expressed in metastatic prostate cancers and its overexpression accelerates prostate tumour progression in mouse models. Here, the author show that that loss of miR-101 and miR-27a in prostate cancer cells can lead to COUP-TFII expression which in turn directly regulates FOXM1 and CENPF favouring prostate cancer metastasis.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38/1 / 38/109 / 38/15 / 38/22 / 38/5 / 38/70 / 38/89 / 38/90 / 631/337/384/331 / 631/67/322 / 631/67/589/466 / 631/80/86 / 64/60 / Animals / Binding sites / Chromosomal Proteins, Non-Histone - genetics / Chromosomal Proteins, Non-Histone - metabolism / COUP Transcription Factor II - genetics / COUP Transcription Factor II - metabolism / Drug resistance / Forkhead Box Protein M1 - genetics / Forkhead Box Protein M1 - metabolism / Humanities and Social Sciences / Humans / Male / Medical prognosis / Medical schools / Medicine / Metastasis / Mice / Mice, Inbred NOD / Microfilament Proteins - genetics / Microfilament Proteins - metabolism / MicroRNAs / MicroRNAs - genetics / MicroRNAs - metabolism / multidisciplinary / Neoplasm Metastasis / Prostate cancer / Prostatic Neoplasms - genetics / Prostatic Neoplasms - metabolism / Prostatic Neoplasms - pathology / Science / Science (multidisciplinary)