Research Article miR-204 Shifts the Epithelial to Mesenchymal Transition in Concert with the Transcription Factors RUNX2, ETS1, and cMYB in Prostate Cancer Cell Line Model Krassimira Todorova, Diana Zasheva, Kristiyan Kanev, and Soren Hayrabedyan Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, 73 Tsarigradsko Shosse Boulevard, 1113 Soia, Bulgaria Correspondence should be addressed to Krassimira Todorova; krasiot@abv.bg Received 29 June 2014; Revised 18 September 2014; Accepted 24 September 2014; Published 14 October 2014 Academic Editor: Vincent J. Gnanapragasam Copyright © 2014 Krassimira Todorova et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Epithelial to mesenchymal transition is an essential step in advanced cancer development. Many master transcription factors shit their expression to drive this process, while noncoding RNAs families like miR-200 are found to restrict it. In this study we investigated how the tumor suppressor miR-204 and several transcription factors modulate main markers of mesenchymal transformation like E- and N-cadherin, SLUG, VEGF, and SOX-9 in prostate cancer cell line model (LNCaP, PC3, VCaP, and NCI- H660). We found that SLUG, E-cadherin, and N-cadherin are diferentially modulated by miR-204, using miR-204 speciic mimics and inhibitors and siRNA gene silencing (RUNX2, ETS-1, and cMYB). he genome perturbation associated TMPRSS2-ERG fusion coincided with shit from tumor-suppressor to tumor-promoting activity of this miRNA. he ability of miR-204 to suppress cancer cell viability and migration was lost in the fusion harboring cell lines. We found diferential E-cadherin splicing corroborating to miR-204 modulatory efects. RUNX2, ETS1, and cMYB are involved in the regulation of E-cadherin, N-cadherin, and VEGFA expression. RUNX2 knockdown results in SOX9 downregulation, while ETS1 and cMYB silencing result in SOX9 upregulation in VCaP cells. heir expression was found to be also methylation dependent. Our study provides means for understanding cancer heterogeneity in regard to adapted therapeutic approaches development. 1. Introduction Prostate cancer is one of the most common malignancies and the second leading cause of death from cancer in men. Androgen receptor (AR) is paramount for the lineage-speciic diferentiation of the prostate, inducing the expression of prostate-speciic genes, such as PSA and TMPRSS2, and maintaining the diferentiated prostate epithelial phenotype [1]. Cellular dediferentiation and epithelial to mesenchymal transition (EMT), by contrast, are a hallmark of malignant transformation and metastatic disease. In this process the reexpression of conserved developmental programs plays a key role [2]. Chromosomal rearrangements fusing the androgen-regulated gene TMPRSS2 to the oncogenic ETS transcription factor ERG occur in approximately 50% of prostate cancers and more than 90% of them overexpress ERG [3]. TMPRSS2-ERG is crucial for cancer progression by disrupting lineage-speciic diferentiation of the prostate and potentiating the histone methyltransferase EZH2-mediated dediferentiation program. ERG disrupts AR signalling by inhibiting AR expression, binding to and inhibiting AR activity at gene-speciic loci, and inducing repressive epige- netic programs via direct activation of the EZH2. he latter causes an epigenetic silencing of developmental regulators and tumor suppressor genes, subverting cancer cells to a stem-cell-like epigenetic state [4]. During this process, part of which is EMT, a transformation of epithelial cells into the invasive and proliferating mesenchymal cells occurs. he main event that follows is the transcriptional shit, involving ETS1, SLUG (SNAI2), and other transcription factors (TF) that suppress the epithelial markers (e.g., E-cadherin and - catenin) and activate mesenchymal ones (e.g., N-cadherin Hindawi Publishing Corporation Journal of Cancer Research Volume 2014, Article ID 840906, 14 pages http://dx.doi.org/10.1155/2014/840906