The influence of fatty acid synthase (FASN) knockdown in the expression of autophagy-related genes in oral squamous cell carcinoma (OSCC) cells.

• Grant number: 22/16712-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): June 01, 2023
• Effective date (End): February 29, 2024
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Edgard Graner
• Grantee: Giulia Marchioreto Pagotto
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

Oral squamous cell carcinoma (OSCC) is the sixteenth most common malignant neoplasm worldwide. Despite recent advances in basic and clinical knowledge about OSCC, 50% of the cases have bad prognosis, with relapse and metastasis. The lipid metabolism, particularly the endogenous fatty acid synthesis, is mediated by the anabolic enzyme fatty acid synthase (FASN) and has been shown to be important for cell survival, proliferation and metastatic spread in OSCC. Our research group has shown the relevance of this pathway in OSCC by both in vitro and animal model experiments, suggesting that FASN activity is a potential target for new pharmacological therapies to control this disease. An intracellular catabolic process that has been suggested as relevant in malignant neoplasms is autophagy, with a still controversial role in OSCC. While some studies describe a high expression of autophagy markers in more aggressive OSCC cases, others show that autophagy has a role in the inhibition of cell proliferation. Therefore, the aim of this project is to verify the influence of FASN knockdown on the expression of autophagy-related genes in OSCC cells. To do that, RT-PCR arrays containing primers to amplificate mRNA associated to autophagy will be used to analyze 3 OSCC cell lines: SCC-9, SCC-9 shFASN-A4C (SCC-9 genetically modified to specifically inhibit FASN) and SCC-9 EVB (Empty Vector as control). The transcripts that show more significantly changes in the expression levels will be confirmed by western blotting and immunoflurescence reactions, with the same cellular lines.