Investigation of lncRNAs and gene regulatory networks modulated by 5-Aza-2´-deoxycytidine in an murine immune-mediated awakening model of dormant melanoma cells

• Grant number: 24/20841-4
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: May 01, 2025
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Miriam Galvonas Jasiulionis
• Grantee: Ianca Rosa Dias
• Supervisor: Gangning Liang
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: University of Southern California (USC), United States
• Associated to the scholarship: 23/17620-3 - Selection and functional analysis of lncRNAs under the effect of DNA methylation involved in tumor progression in an immune-mediated dormancy model, BP.MS

Abstract

This project aims to examine the role of long non-coding RNAs (lncRNAs) regulated by DNA methylation in melanoma progression and immune-mediated tumor dormancy, focusing on the effects of 5-Aza-2'-deoxycytidine, a DNA demethylating agent, on lncRNA modulation within the tumor microenvironment (TME). Previous studies showed that 5-Aza-2'-deoxycytidine reduces tumor volume and delays tumor formation, suggesting that it activates immune responses supporting tumor control via a regulatory RNA network. Key lncRNAs, such as H19, SNHG17, and Mir22HG, are significantly differentially expressed in the TME following treatment and are currently under functional investigation. Preliminary data indicates that the drug effects differ between TME and tumor cells, necessitating deeper analysis of lncRNAs involved in immune activation as possible trans-regulatory targets. For that, we propose in vivo experiments, RNA sequencing, Differential Gene Expression (DGE) analysis, Weighted Correlation Network Analysis (WGCNA), and Gene Ontology (GO) to understand the influence of this drug on lncRNA expression, uncovering potential immune and tumor regulators. The goal is to identify lncRNAs as therapeutic targets or biomarkers to predict recurrence, especially in solid tumors where relapse is common. Collaborating with Dr. Gangning Liang at USC, an expert in cancer epigenetics, will enhance the clinical relevance of the findings.