Decoding stem cell-associated long non-coding RNAs in glioma heterogeneous subpopulations via single-cell and network-based approaches

• Grant number: 25/08370-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: October 01, 2025
• End date: May 31, 2026
• Field of knowledge: Biological Sciences - Genetics
• Principal Investigator: Eduardo Moraes Rego Reis
• Grantee: Daniela Bizinelli
• Supervisor: Michele Ceccarelli
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Miami, United States
• Associated to the scholarship: 24/02910-9 - Identification of long non-coding RNAs associated with tumor stemness in pancreatic cancer, glioblastoma, and melanoma, BP.DR

Abstract

Gliomas are among the most therapeutically challenging central nervous system malignancies, with both IDH-mutant (IDHmut) and IDH-wildtype (IDHwt) subtypes exhibiting poor prognoses and limited treatment options. Despite advances in molecular classification, glioma stem cells (GSCs) remain key drivers of therapeutic resistance. This study investigates long non-coding RNAs (lncRNAs) as critical regulators of GSC maintenance and potential therapeutic targets. Using an integrative computational approach, we will analyze single-cell RNA sequencing (scRNA-seq) data from over 17,000 tumor cells to: (1) map differentiation trajectories and identify stemness-associated lncRNAs; (2) construct gene co-expression networks to uncover functional lncRNA modules; (3) characterize lncRNA-mediated ligand-receptor interactions; and (4) distinguish conserved and subtype-specific lncRNA signatures in IDHmut and IDHwt gliomas. The expression of candidate lncRNAs will be evaluated in bulk tissue RNAseq data from clinical samples to assess their prognostic significance. By deciphering lncRNA regulatory networks in GSCs, this study aims to identify novel therapeutic targets to overcome treatment resistance in gliomas. These findings could contribute to the development of precision oncology strategies, with potential translational applications in other aggressive and chemoresistant cancers. (AU)