Functional assessment of the roles of oncogenic lncRNAs in Pancreatic Ductal Adenocarcinoma using omics integrative approaches.

• Grant number: 23/00231-4
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: November 01, 2023
• End date: March 31, 2028
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Eduardo Moraes Rego Reis
• Grantee: Maria Eduarda Mazzi Esquinca
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Pancreatic ductaladenocarcinoma (PCA) is a highly lethal cancer for which there are no effectivetherapies. Omics approaches have been widely used to characterize the molecularprofile of PCA in search of vulnerabilities that indicate new targets fortreatment. Long non-coding RNAs (LncRNAs) are encoded by 60% of human genes andcan regulate several cellular processes, such as chromatin regulation,transcriptional and post-transcriptional/translational control. Several studieshave pointed to critical lncRNAs thatsupport tumor phenotypes and tumorprogression, acting in the regulation of genes that control proliferation,migration, cell invasion, apoptosis, and may be associated withchemoresistance. A current scientific challenge is the identification of the mechanismsand molecular pathways dependent on the expression of lncRNAs in tumor cells.In this work, we will perform a metabolomics and proteomics analysis to deepenthe knowledge about the mechanisms of action of five lncRNAs with oncogenicproperties in the PCA, previously identified in our research group (LINC01559,LINC01133, CCAT1, LINC00920 and UCA1). Through the integrative analysis of datagenerated after the silencing of these transcripts in PCA cell lines, we hopeto identify molecular and metabolic pathways dependent on the expression ofthese lncRNAs. In addition, the relationship of these lncRNAs withchemoresistance to gemcitabine, the main drug used in the treatment of patientswith pancreatic cancer, will be evaluated. Through integrative bioinformaticsanalyzes followed by in vitro validation, we will seek to identify cellularprocesses and metabolic pathways that are associated with the aggressiveness ofPCA and that are dependent on the expression of lncRNAs, and thus point out newpossible targets and strategies for disease therapy. (AU)