Dysregulation of miRNAs-COUP-TFII-FOXM1-CENPF axis contributes to the metastasis of prostate cancer.
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.
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Physiology, College of Medicine, National Cheng Kung University, Tainan Taiwan 701, ROC.
Shih-Chieh
SC
Lin
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Chung-Yang
CY
Kao
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Hui-Ju
HJ
Lee
Department of Medicine, Dan L. Duncan Cancer Center Division of Biostatistics, Baylor College of Medicine, Houston, Texas77030, USA.
Chad J
CJ
Creighton
Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
Michael M
MM
Ittmann
Department of Physiology, College of Medicine, National Cheng Kung University, Tainan Taiwan 701, ROC.|Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan Taiwan 701, ROC.
Shaw-Jenq
0000-0002-3569-5813
SJ
Tsai
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Medicine and Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Sophia Y
SY
Tsai
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Medicine and Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Ming-Jer
MJ
Tsai
D000818:Animals; D051837:COUP Transcription Factor II / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D000072278:Forkhead Box Protein M1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D051837:COUP Transcription Factor II; D002868:Chromosomal Proteins, Non-Histone; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; C534072:MIRN101 microRNA, human; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D008840:Microfilament Proteins; C094772:centromere protein F