Human PRNP gene transcription factors characterization as possible therapeutic targets: anti-tumoral strategies against glioblastoma.

• Grant number: 23/12717-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): December 01, 2023
• Effective date (End): November 30, 2024
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Marilene Hohmuth Lopes
• Grantee: Breno Pereira de Sousa
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/15557-4 - Prion protein and its partners: emerging targets for glioblastoma stem cell based-therapy, AP.JP2

Abstract

The glioblastoma (GBM) is an extremely lethal brain tumor in adults for which there is no effective therapy. Many factors contribute to its aggressiveness, namely the high cellular and molecular heterogeneity and the presence of glioblastoma stem-cells (GSCs), crucial for the treatment resistance and tumor recurrence. Several evidence shows that the gene expression of the cellular prion protein (PrPC) is elevated in GBM when compared to less aggressive tumors, such as IDH-mutant astrocytomas. Data obtained by our group shows that PrPC has an important role in GSCs, acting as a scaffold protein, integrating signaling platforms, modulating proliferation and self-renewal of these cells. Once the mechanisms that regulate the overexpression of PrPC in GBM remain unknown, this paper intends to identify the transcription factors (TFs) which bind to the promoter region of the gene of PrPC (human PRNP gene), in order to provide information about TFs regulatory networks that can reveal potential targets for the development of newer and more effective anti-tumoral therapies.