Determination and analysis of gene regulation network of angiogenesis in a murine model

• Grant number: 19/05287-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): December 01, 2019
• Effective date (End): June 30, 2022
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: João Carlos Setubal
• Grantee: Jhonatas Sirino Monteiro
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Angiogenesis is the process which new blood vessels form from pre-existing vessels. Many diseases are dependent of neovascularization to growth in the organism, like Cancer and retinopathies. These diseases are known as angiogenesis-dependent diseases. The formation of blood vessels in a adult organism occur under delicate control of gene expression, and dysregulation of this process could entail in severe diseases like, retinopathy of prematurity and diabetic retinopathy. It is known that Vascular Endothelial Growth Factor (VEGF) is one of the main components that regulates angiogenesis, and that's why this factor became a therapeutic target for Cancer treatment. However, this therapies, although effective, presented collateral effects, because VEGF is also a survival factor for quiescent endothelial cells. And an important fraction of the patients become resistant to anti-VEGF treatment. For this reason, studies are searching for new therapies more efficient and with minimum collateral effects. Understand the mechanisms of gene regulation of this process could contribute for a better understanding of angiogenesis mechanisms. Our group generated RNA-Seq data from retinas of a murine model of Oxygen-Induced Retinopathy (OIR), one of the animal models that better mimics angiogenesis in vivo (Guarischi-Souza, manuscript submitted, attached to proposal). The first step of this study were analyzed Differentially Expressed Genes (DEG) between samples of induced and not-induced angiogenesis, which were identified 153 DEGs. 11 of 153 DEGs were used to develop a gene signature as a prognostic molecular biomarker for prediction of Breast Cancer relapse. This indicates that the murine model and the transcriptome generated by our group recapitulate the molecular processes involved in human angiogenesis. For this reason, in this project, we will expand these studies and analyze the role of mRNA isoforms and non-coding RNAs (lncRNA, miRNA and circRNA) in neovascularization. The final goal is to build networks of interaction between non-coding RNAs and mRNAs that represents the gene regulatory network of blood vessels formation with emphasis in pathological angiogenesis. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE PEDRO-JOVE, R.; PUIGVERT, M.; SEBASTIA, P.; MACHO, A. P.; MONTEIRO, J. S.; COLL, N. S.; SETUBAL, J. C.; VALLS, M.. Dynamic expression of Ralstonia solanacearum virulence factors and metabolism-controlling genes during plant infection. BMC Genomics, v. 22, n. 1, MAR 9 2021. (19/05287-2)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MONTEIRO, Jhonatas Sirino. Investigations into the molecular mechanisms of angiogenesis based on gene expression data in a murine model, and its application in breast cancer prognosis. 2022. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Matemática e Estatística (IME/SBI) São Paulo.