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Functional high-throughput screening for the identification of microRNAs with antitumor and antimetastatic potential in head and neck cancer

Grant number: 14/20756-5
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2015
Effective date (End): July 31, 2017
Field of knowledge:Health Sciences - Medicine
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Rodrigo Alexandre Panepucci
Grantee:Bruno Braga Sangiorgi
Home Institution: Hemocentro de Ribeirão Preto. Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP (HCMRP). Secretaria da Saúde (São Paulo - Estado). Ribeirão Preto , SP, Brazil
Associated research grant:13/08135-2 - CTC - Center for Cell-Based Therapy, AP.CEPID

Abstract

The head and neck cancer (HNC) is a worldwide public health issue, affecting thousands of people each year, whose mortality rate has remained virtually unchanged in the last decades. In order to seek new and more effective therapeutic approaches against cancer, microRNAs (miRs) have received great attention in view of the ability of these molecules to bind to a hundreds of target transcripts, regulating their translation or inducing their degradation. In this project, we propose to identify molecular pathways with potential as therapeutic targets, or even molecules of miRs with possible use as therapeutic agents in the treatment of these cancers. For this, HNC cell lines will be transfected with mimetic synthetic molecules (pre-miRs) or inhibitory (anti-miRs) of miRs. Following transfection, we will use an experimental approach High-content screening - HCS, based on automated computer acquisition and image analysis of fluorescence microscopy, which allows qualitative and quantitative analysis of a large number of morphological and functional parameters, including the assessment of proliferation and cell death, as well as processes of Epithelial-Mesenchymal transition (EMT) and Mesenchymal-Epithelial transition (MET), involved on cancer cells migration and attachment in secondary foci, respectively. After evaluation of these parameters, molecules with significant effects will be evaluated for their activity on cell migration. The transcriptional profiles of cells transfected with such molecules will be determined with the use of microarrays, in order to identify pathways and processes modulated. The results of this project will enable a greater understanding of the role of microRNAs in processes relevant to the pathophysiology of CCP, and may serve as the basis for the identification of candidate targets for the development of new therapeutic approaches. (AU)