Expression of microRNAs miR-20b, miR-125b and miR-145 in breast carcinomas with MUC1 overexpression

• Grant number: 12/05112-9
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2012
• End date: August 31, 2014
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Alfredo Ribeiro da Silva
• Grantee: Alfredo Ribeiro da Silva
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Mucin 1 may behave as an oncogene and may perform an important role during breast cancer development. Recently, our research group showed that MUC1 is overexpressed in invasive breast ductal carcinoma and that this oncogene could be involved in hypoxia regulation through differential expression of HIF-1± (hypoxia-inducible factor-1±). The purpose of this study is to investigate the possible action of microRNAs (miRNAs) in this event. miRNAs are a group of non coding RNAs (21-23 nucleotides) that regulate the gene expression. The majority of studies concerning the role of miRNAs in breast cancer have been done with cell cultures derivate from primary tumor or metastasis. In cell cultures, the miRNAs miR-125b and miR-145 have the gene MUC1 as target, while the miR-20b has HIF-1± and STAT3 (signal tranducer and activator of transcription 3) as target. In this work, we will investigate the expression of the microRNAs miR-20b, miR125b and miR-145, and the expression of their respective targets, in formalin fixed paraffin embedded samples from patients' biopsies with invasive breast ductal carcinomas with MUC1 overexpression. To achieve ou goal, the following techniques will be perform: immunohistochemistry analyses, for verification of MUC1, HIF-1± and STAT3 protein expression; in situ hybridization for verification of co-location of MUC1 and its respective miRNAs; RT-PCR for evaluating the miR-20b, miR-125b and miR-145 expression; and Western blot for quantification of MUC1, HIF-1± and STAT3 proteins. The demonstration that these miRNAs can regulate, in FFPE samples, targets related to tumor hypoxia can contribute for a better understanting of molecular mechanisms involved in HIF-1± expression in breast invasive ductal carcinomas with MUC1 overexpression. (AU)