Identification of long non-coding RNAs associated with tumor stemness in pancreatic cancer, glioblastoma, and melanoma

• Grant number: 24/02910-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2024
• End date: February 28, 2027
• Field of knowledge: Biological Sciences - Genetics
• Principal Investigator: Eduardo Moraes Rego Reis
• Grantee: Daniela Bizinelli
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Pancreatic cancer, glioblastoma, and melanoma pose significant challenges in the oncology field, with considerable mortality rates and complexities in clinical management. Despite advancements in understanding tumorigenic mechanisms, therapeutic resistance, especially related to cancer stem cells (CSCs), remains an obstacle. Considering the impact of long non-coding RNAs (lncRNAs) on biological processes associated with CSC maintenance, this project proposes an innovative approach to explore these molecules as targets capable of negatively modulating malignant phenotypes associated with stemness in these cancers. The methodological steps mainly comprise 1) application of a previously published and validated supervised prediction model to obtain the stemness index of each tumor sample evaluated, 2) identification of differentially expressed (DE) lncRNAs between sample groups characterized with low or high degrees of stemness index; 3) investigation of stemness-related lncRNA expression concerning the presence of different cellular subtypes from tumor microenvironment and along the tumor cell differentiation trajectory in single-cell data, and 4) association with clinical parameters. In this way, we aim to fill gaps in the understanding of the molecular mechanisms underlying CSCs and identify new targets for the development of therapeutic strategies capable of eradicating these tumor cell subpopulations and preventing metastatic dissemination and chemoresistance in patients with aggressive cancers.