Characterizing prognostic significance and molecular mechanisms associated with interleukin 17F (IL-17F) and its receptor IL-17RC in oral squamous cell carcinoma

• Grant number: 23/10632-6
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: January 01, 2024
• End date: December 31, 2027
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Ricardo Della Coletta
• Grantee: Bruno Cesar da Costa
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

The lack of consistent biomarkers for oral squamous cell carcinoma (OSCC) represents a major obstacle to individualizing treatment. Recently, interleukin 17F (IL-17F) has been implicated in the development of cancers in different organs. In OSCC, IL-17F levels were associated with a better prognosis and demonstrated predominantly antitumor effects, however, an association with disease progression was also found. To investigate the prognostic value of IL-17F and its receptor IL-17RC, we evaluated the expression of IL-17F and IL-17RC in samples from the TCGA database (The Cancer Genome Atlas) and the results revealed a great potential of these proteins as diagnostic and prognostic markers. In order to expand our knowledge about the role of this interleukin in oral tumorigenesis, the aim of this project is to investigate the prognostic value and biological role of IL-17F and its receptor IL-17RC in OSCC. For this purpose, IL-17F and IL-17RC expressions will be evaluated by immunohistochemistry in two independent cohorts. Loss- or gain-of-function strategies will be applied in OSCC cell lines to determine the impact of IL-17F and IL-17RC on viability, proliferation, apoptosis, migration, invasion, epithelial-mesenchymal transition properties and modulation of response to chemotherapy, radiotherapy and targeted therapy. The zebrafish model will also be used to analyze tumor formation and metastasis. Furthermore, we will study the role of IL-17F/IL-17RC signaling in the cross-talk between cancer cells and immune cells using a microfluidic chip. Finally, the regulation of IL-17F and IL-17RC by microRNAs will be explored by bioinformatics and functional assays. It is expected that this study can elucidate the importance and the mechanisms through which IL-17F and IL-17RC exert their effects in OSCC, opening perspectives for their use as prognostic biomarkers and therapeutic targets for oral cancer.