Differential expression genes and mRNA-miRNA network by microarray analysis in the Leishmania donovani Infected mouse liver samples
Differential expression genes and mRNA-miRNA network by microarray analysis in the Leishmania donovani Infected mouse liver samples
Ali Ghaneh,1,*
1. Department of Sciences and Biotechnology, Shahid Ashrafi Isfahani University, Isfahan, Iran
Introduction: Leishmania donovani induces visceral leishmaniasis (VL) where the protozoan invades and dwells within hepatic and splenic tissue macrophages. Considering the anomalous lipid profile noted in VL patients, we investigated the status of serum fats in an experimental murine model of VL. The murine VL liver exhibited modified expression of lipid metabolic genes, numerous of which are direct or indirect targets of the liver-specific microRNA-122. A concurrent decrease of miR-122 expression was noted in the VL liver. (1)
Leishmania donovani invades and seizes the microRNA import-export apparatus of host macrophages and thrives by transmitting the host-derived miR-146a to adjacent cells and halts inflammation. (2)
Methods: The GSE38985 gene expression profile data were downloaded from the NCBI Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo). The present study included a total of 5 samples, which comprised 2 Leishmania donovani-infected mouse liver and 3 normal adjacent tissues. Using GEO2R, an indepth analysis was performed to obtain differentially expressed genes. The most significant genes (|logFC| > 2 and adjusted p-value< 0.05) were selected and taken to miRWalk 2.0 to find target miRNAs and hub genes.
Results: According to GEO analysis of GSE38985 were indicated 1091 up and downregulated genes (Fig 1). Among all these genes Hsd3b5, Ubd, and Mgst2 were considered an Up-regulated gene that related to VL. This examination revealed that the GSE38985 was remarkably enriched in multiple biological processes. The potential central genes were investigated in Kyoto Encyclopedia of Genes and Genomes (KEGG) repository to identify the pathways in which they are individually involved.
Ubd is present in essential genes for Activation G protein gated potassium of cell. We watched that Leishmania donovani disease driven to improved N-Ras expression, though it repressed K-Ras and H-Ras expression. L donovani contamination too expanded extracellular signal-regulated kinase 1/2 phosphorylation and at the same time diminished p38 phosphorylation. (7)(8) (9) Fig3 (B)
Mgst2 is present in essential genes for the Glutation metabolism of cells. (10)(11)
Glutathione is a powerful antioxidant that helps protect cells from damage caused by harmful molecules in the body. In trypanosomes and leishmanias, trypanothione helps protect the parasite from the mammalian host's immune system by recycling it through an enzyme called trypanothione reductase.(10)(11)(12)
Conclusion: In summary, this finding could be suggested novel interactions among micRNAs and mRNA(miR-146a , microRNA-122, Hsd3b5, Ubd, Mgst2 for the candidate diagnostic and prognostic markers associated by bioinformatics analysis.
We believe that, without any severe negative side effects, this ceRNA network could be used as a potential tool for both preventative.