Abstract
Abstract Prostate Cancer (CaP) is the most common non-cutaneous form of cancer in men. It is also the second leading cause of cancer mortality in men in the USA. Oncogenic activation of the ETS Related Gene (ERG) as a result of gene fusions is the most common genomic alteration in prostate cancer reported to date. ERG has a milieu of transcriptional targets that regulate genes involved in various cellular processes including oncogenesis, inflammation, cell invasion, and DNA damage. Moreover, knockdown (KD) of ERG in TMPRSS2-ERG expressing CaP cells (VCaP) suppresses the growth and invasiveness of VCaP cells and in xenograft models. ERG protein has been implicated as a key player in the progression from pre-invasive to invasive disease status of CaP. Therefore, understanding mechanisms by which ERG promotes CaP progression is essential for developing novel prognostic/therapeutic targets for CaP. Our analyses of miRNA expressions in the human TMPRSS2-ERG fusion harboring VCaP cells compared to ERG-suppressed (with siRNA against ERG) VCaP controls indicate altered expression of miRNAs. Interestingly, we find that ERG suppresses the expression of miR-449a, which has been shown to regulate proliferation of CaP cells. In silico analyses (IPA and Genomatix) of cellular pathways targeted by these miRs focus on regulatory networks that are indicative of EMT and include molecules like DES (desmin), PDGFRA (platelet-derived growth factor receptor, alpha polypeptide) and TGFBR1 (transforming growth factor beta receptor 1). These pathways are potential candidate therapeutic targets. These data form the basis of new insights into the miRNA alterations in the context of major oncogenic activation in prostate cancer. Moreover, these miRNAs will provide novel prognostic marker and therapeutic targets for prostate cancer and will ultimately define CaP associated miRNAs in the context of ERG positive and ERG negative prostate cancers. Supported by: United States Military Cancer Institute [RB] and [SS]. Citation Format: Parameet Kumar, Albert Dobi, George Petrovics, Ahmed Mohamed, Shiv Srivastava, Roopa Biswas. Role of microRNAs in the development of prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5342. doi:10.1158/1538-7445.AM2013-5342
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