Investigation of the role of small peptides in glioblastoma

• Grant number: 25/04531-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2025
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: João Carlos Setubal
• Grantee: Luiza Dias Marques
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The glioblastoma multiforme (GBM) is an aggressive and challenging-to-treat brain tumor, with resistance attributed to complex molecular processes such as DNA repair and transcriptional and translational dysregulation. Recently, long non-coding RNAs (lncRNAs) have emerged as key regulators in GBM, particularly due to their potential to encode small peptides (SEPs) through small open reading frames (sORFs). These peptides have relevant biological functions, including the regulation of tumor pathways, making them potential therapeutic targets. This study aims to integrate transcriptomic and proteomic approaches to characterize SEP-encoding lncRNAs and their interactions within the translational landscape of GBM for the identification of potential therapeutic targets. Using polysome profiling data from model cell lines, differentially expressed lncRNAs with translational potential will be identified. Functional analysis will reveal the biological pathways associated with these lncRNAs and their peptides. Co-expression networks will be constructed to infer regulatory mechanisms. Proteomic validation will be conducted using mass spectrometry data, employing the moPepGen algorithm to detect non-canonical peptides. Finally, integration with clinico-pathological data from The Cancer Genome Atlas (TCGA) will allow the assessment of the prognostic relevance of these molecules. By elucidating the translation and functional role of SEPs derived from lncRNAs, this study seeks to identify novel biomarker targets and potential therapeutic strategies for GBM.