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 Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2015
• End date: July 31, 2017
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Rodrigo Alexandre Panepucci
• Grantee: Bruno Braga Sangiorgi
• Host 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)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SANGIORGI, Bruno Braga. The high-content screening approach for the identification of miRs with therapeutic potential in head and neck cancer. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.