The role of GATA3 in the regulation of high-risk HPV transcription and differentiation of human keratinocytes

• Grant number: 23/12249-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: November 20, 2023
• End date: May 14, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Laura Cristina Sichero Vettorazzo
• Grantee: Valéria Talpe Nunes
• Supervisor: John Doorbar
• Host Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Institution abroad: University of Cambridge, England
• Associated to the scholarship: 19/05141-8 - Identification of transcription factors with potential therapeutic effect in cells infected by different variants of HPVs 18 and 16, BP.DD

Abstract

The life cycle of human papillomaviruses is deeply correlated with the differentiation process of the squamous epithelium, with the transcriptional activity and production of the oncoproteins E6 and E7 being regulated by cellular transcription factors. Our current data shows that the transcription factor GATA3 is a negative regulator of HPV transcription and may have a role in the tumorigenesis mediated by HPV in the cervical tissue. Further analysis of the in vivo cellular localization and protein levels of GATA3 and viral transcripts could importantly corroborate our data and give important information concerning viral transcriptional regulation in the context of the differentiation of the infected epithelium. The fluorescence microscopy and RNAScope methodologies are powerful tools to investigate these molecular interactions, thus obtaining high-resolution imaging that can show the physical interactions of molecular processes with precision and corroborate the data obtained by other methodologies. (AU)