Functional evaluation in the control of gene expression profile of breast cancer cell lines.

• Grant number: 11/23348-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2012
• End date: May 31, 2014
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Márcia Maria Chiquitelli Marques Silveira
• Grantee: Adriane Feijó Evangelista
• Host Institution: Hospital do Câncer de Barretos. Barretos , SP, Brazil

Abstract

New insights into the molecular biology arise from microRNA post-transcriptional regulation concepts and their role described in the process of angiogenesis, invasion, migration and tumor metastasis, new perspectives arise in the target prediction for further therapies. According to these evidences, this study follows the line of functional genomics applied to molecular oncology field with a focus on system biology and refers to the role of microRNAs in the modulation of gene expression profiling in breast cancer cell lines. Initially it will be performed the expression profiles identification from coding messenger RNAs (RNAm) and microRNAs by microarray technology from breast cancer cell lines. In addition, bioinformatics programs will be applied (hierarchical cluster analysis for statistical significance and construction of gene networks) to measurement the RNAm and microRNAs expression, because we conceive that complex process such as angiogenesis, cell migration and invasion will only be better understood by means of large-scale functional genomics. The central ideia is obtain the differential expression signatures and trying to stabilish networks between messenger RNAs and microRNAs in order to select potential microRNAs to take part of knockdown in vitro and the evaluation of the molecular and cell effects. The prediction of microRNAs for knockdown and its molecular effects will be analyzed by several bioinformatics tools intending to (i) identification of new miRNA-mRNA interactions, involved with invasion, migration and/or metastasis; (ii) identification of gene (mRNA) expression profiles after and before the knockdown; (iii) identification of canonical pathways after and before the knockdown to evaluate the mechanisms affected. In addition, it will be performed cell assays to check the cellular effects after knockdown which could be of interest for cancer therapy, such as invasion, migration, viability, citotoxicity and apoptosis. The results of this study will be useful to a better understanding from genetic-molecular and celular bases of microRNAs role in breast cancer, as well as with the identification of further targets to therapies. (AU)