Investigation of RhoA and RhoC silencing effects on the activation of cell cycle and apoptosis signaling pathways in leukemia cells treated with UV-C.

• Grant number: 23/03139-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2023
• End date: June 30, 2025
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Mariana Lazarini
• Grantee: Caroline Santos de Souza
• 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 neoplasia caused by blockage of myeloid hematopoietic cell differentiation and consequent accumulation of blasts in the bone-marrow. AML is characterized by low survival rates and the presence of TP53 gene mutations found in approximately 10% of the cases are related with worse prognosis. Moreover, dysregulation of the p53 signaling pathway is found in additional patients through other mechanisms. Cell-cycle interruption and apoptosis are cellular responses mediated by p53 essential to tumor suppression. RhoA and RhoC Rho GTPases proteins are highly expressed in human tumors and have been related to the regulation of p53, signaling. The aim of this project is to investigate the effects of RhoA and RhoC knockdown in the activation of cell-cycle and apoptosis signaling pathways in leukemia cells. For this purpose, the expression of cell cycle and apoptosis regulators will be investigated by western blot in MOLM-13 (wild-type TP53) and U937 (mutated TP53) cells stably silenced for RhoA or RhoC and treated with UV-C light. The results of this study will contribute to elucidate the role of RhoA and RhoC in the p53 signaling pathway, as well as their effects in cell-cycle and apoptosis.