Abstract 3094: MiRNAs 484 and 210 control Pax-5 expression and function in breast cancer.

Abstract

Abstract Every hour, approximately 21 people are diagnosed with cancer where 9 will succumb to their disease. Recent studies have enabled the identification of important factors regulating cancer progression, one of these being the Pax-5 gene. Pax-5, an essential developmental factor, is aberrantly expressed in various B cell cancer lesions and solid tumors such as carcinoma. Although Pax-5 downstream activity is well characterized, the regulation of aberrant Pax-5 expression in a cancer specific context is poorly understood. To investigate the regulation of Pax-5 expression, we turned our attention to micro-RNAs (miRNAs). MiRNAs are highly conserved, small non-coding RNA molecules that regulate key biological processes. Extensive studies also show their deregulation in multiple cancer lesions. This study aims to elucidate a correlation between differentially expressed miRNAs in cancer cells and deregulated Pax-5 expression levels. Using bioinformatics platforms we observe that miRNAs 484, and 210 are aberrantly expressed in breast cancer cells and cross-reference with their capacity to target the Pax-5 mRNA 3’ untranslated region (UTR 3’). Using anti-miRNAs transfected into Pax-5 expressing breast cancer cell lines (MCF-7 and MB231), we demonstrate that miRNAs 484 and 210 are capable of regulating Pax-5 expression. In addition, miRNA-regulated Pax-5 expression resulted in a concomitant alteration in Pax-5-dependant phenotype and cancer processes. This is the first study demonstrating the regulation of Pax-5 expression and function by non-coding RNAs in cancer cells. We believe that the aberrant expression of Pax-5 in cancer cells is in part due to deregulated miRNA expression profiles. This study will bring insight in regards to cancer regulating processes associated with miRNA and Pax-5 deregulations, thus helping us to better understand the aberrant Pax-5 expression levels within cancerous states. This study can therefore provide the eventual possibility of earlier, more efficient diagnostics as well as more targeted treatments for cancer patients. Citation Format: Jason M. Harquail, Gilles A. Robichaud. MiRNAs 484 and 210 control Pax-5 expression and function in breast 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 3094. doi:10.1158/1538-7445.AM2013-3094