Influence of fatty acid synthase (FASN) silencing on the expression of autophagy-related genes in an oral squamous cell carcinoma cell line.

• Grant number: 24/22800-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2025
• End date: December 31, 2025
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Edgard Graner
• Grantee: Nicole Alves da Silva
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity, affecting more frequently the lateral border of the tongue and the floor of the mouth. Its prognosis largely depends on the extent of regional lymph node involvement and presenceof distant metastases, with a low overall survival rate (around 33%). Previous studies from ourgroup and others have shown enhanced levels of the metabolic enzyme fatty acid synthase (FASN), responsible for the endogenous synthesis of fatty acids, in OSCC cells. FASN seems to be essential for both proliferation and survival of malignant cells originated from various tissues. We recently demonstrated, through in vitro studies, that FASN inhibition promotes apoptosis and necrosis in cancer cells. However, taken together, these two forms of cell death do not fully explain the death of a large percentage of cells. Autophagy appears to play a dual biological role in tumor cells since some studies suggest that it induces cell death and others point to a protective function. In search of a potential relationship between FASN activity and the autophagic pathway, our group recently exploited two OSCC cell lines: SCC-9 (parental) and SCC-9 sh-FASN (with FASN genetically silenced). Total RNA was isolated from the silenced cell line and analyzed by using a qRT-PCR array containing primers specific for genes directly related to autophagy. The results obtained were compared with in silico data (from the public biological database Depmap) of expression rates of the same genes in the parental cell line. From this analysis, six genes were selected: ATG4A, ATG5, ATG9A, ATG10, SQSTM1,and MAP1LC3B (corresponding to LC3BI and LC3BII), all of them highly expressed by the FASN-silenced cell line, except for SQSTM1, which was more expressed in the parental cells, suggesting that FASN inhibition directly influence autophagy. The present study aims to quantify the expression rates of these genes in SCC-9 and SCC-9 sh-FASN cells and, for those with great variations, the amount of their respective protein products.