Investigation of the effects of RhoA and RhoC proteins silencing in proliferation and migration of myeloid cell lines

• Grant number: 23/11291-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2023
• End date: June 30, 2024
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Mariana Lazarini
• Grantee: Guilherme Ramos Sales de Mendonça
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Acute Myeloid Leukemia (AML) is a highly heterogeneous bone marrow cancer, characterized by biochemical dysregulation that results from molecular changes in stem and progenitor cells of the hematopoietic system. These changes cause a block in cell differentiation with the accumulation of immature cells in the bone marrow and/or peripheral blood, compromising blood cell production. AML treatment is usually nonspecific and associated to low patient survival rates. RhoA and RhoC are homologous proteins of the protein family of Rho GTPases involved in cell processes related to the cytoskeleton organization, such as proliferation and migration. RhoA and RhoC are dysregulated in human cancers, but their functions were not explored in AML.In this project, we will investigate the role of RhoA and RhoC proteins in the proliferation and migration of leukemia cells. Proliferation and migration will be evaluated in U937 and OCI-AML3 cell lines silenced for RhoA or RhoC. The proliferation and migration assays will first be standardized in parental cell lines and then performed in cells silenced with specific lentivirus for the inhibition of RhoA and RhoC. Results from this project with additional data from our group will contribute to the elucidation of the role of RhoA and RhoC proteins in the proliferation and migration capacities of neoplastic myeloid cells.