Characterization of homeobox gene Cux1 and its intronic microRNA miR-721 in murine macrophages infected with Leishmania amazonensis

• Grant number: 18/18499-5
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): November 01, 2018
• Effective date (End): June 30, 2021
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Sandra Marcia Muxel
• Grantee: Camilla de Almeida Bento
• Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The protozoan Leishmania can subvert the immune response against intracellular pathogens through the regulation of gene expression, such as transcriptional and post-transcriptional mechanisms for the establishment of the infection. The transcriptional mechanisms occur through the action of transcription factors, which can bind to the promoter region of the gene, inducing its transcription. Moreover, post-transcriptional mechanisms can be mediated by microRNAs, these are small non-coding RNAs with approximately 20 nucleotides, they can bind to the 3'-UTR region of the target gene's mRNA and block protein synthesis or its cleavage through the miRISC complex, thus silencing gene expression. Leishmania can alter the expression profile of microRNAs of the host's macrophages to subvert the microbicide response, thus allowing the survival and proliferation of the parasite. This project aims to study the connection between the transcription factor gene Cux1 and miR-721, transcribed from the intronic region of Cux1, and their targets in BALB/C mice macrophages infected by L. amazonensis. Our study will allow the analysis of inter-regulation between both modulators and their actions in composing the inflammatory response, focusing on the L-arginine metabolization pathway for the production of nitric oxide by induction of nitric oxide synthase (NOS2).