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TMPRSS2-ERG Gene Fusions Induce Prostate Tumorigenesis by Modulating MicroRNA MiR-200c

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Journal Oncogene
Date 2013 Nov 5
PMID 24186205
Citations 25
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Abstract

Chromosomal translocations that juxtapose the androgen-sensitive transmembrane protease, serine 2 (TMPRSS2) gene promoter to the oncogenic ETS-family transcription factor ERG result in excessive ERG overexpression in approximately 50% of prostate cancer (PCa) patients. Although numerous studies have investigated ERG-downstream genes, such studies have not attempted to examine miRNAs, which however are emerging to be important regulators of cancer. Through bioinformatics analysis of ChIP-Seq ERG data and miRNA expression profiling data we nominated miR-200c as a direct target of ERG. Experimentation of PCa cells with ERG overexpression or knockdown demonstrated that ERG directly repressed miR-200c expression by physically binding to the erythroblast transformation-specific (ETS) motif within its promoter. Consequently, miR-200c was downregulated in ERG-positive PCa, and miR-200c target gene expression was restored. In addition, the expression pattern of miR-200c target genes predicted ERG status in clinical PCa specimens. Furthermore, miR-200c was found to be important in modulating ZEB1 upregulation by ERG. Most importantly, miR-200c reconstitution fully reversed ERG-induced epithelial-to-mesenchymal transition (EMT), cell migration and invasion. Therefore, our study report miR-200c as the first miRNA target of ERG and a critical inhibitor of PCa cell motility. Therapeutic delivery of miR-200c may provide personalized treatment for patients with the molecular subtype of PCa that harbors TMPRSS2-ERG gene fusions.

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References
1.
Clark J, Merson S, Jhavar S, Flohr P, Edwards S, Foster C . Diversity of TMPRSS2-ERG fusion transcripts in the human prostate. Oncogene. 2006; 26(18):2667-73. DOI: 10.1038/sj.onc.1210070. View

2.
Rokavec M, Wu W, Luo J . IL6-mediated suppression of miR-200c directs constitutive activation of inflammatory signaling circuit driving transformation and tumorigenesis. Mol Cell. 2012; 45(6):777-89. PMC: 3319241. DOI: 10.1016/j.molcel.2012.01.015. View

3.
Yu J, Cao Q, Mehra R, Laxman B, Yu J, Tomlins S . Integrative genomics analysis reveals silencing of beta-adrenergic signaling by polycomb in prostate cancer. Cancer Cell. 2007; 12(5):419-31. DOI: 10.1016/j.ccr.2007.10.016. View

4.
Volinia S, Calin G, Liu C, Ambs S, Cimmino A, Petrocca F . A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006; 103(7):2257-61. PMC: 1413718. DOI: 10.1073/pnas.0510565103. View

5.
Grasso C, Wu Y, Robinson D, Cao X, Dhanasekaran S, Khan A . The mutational landscape of lethal castration-resistant prostate cancer. Nature. 2012; 487(7406):239-43. PMC: 3396711. DOI: 10.1038/nature11125. View