Sarmistha Adhikari1, Paramita Mandal2. 1. Biomedical Genetics Laboratory, Department of Zoology, The University of Burdwan, West Bengal, India. 2. Biomedical Genetics Laboratory, Department of Zoology, The University of Burdwan, West Bengal, India. Electronic address: pmandal@zoo.buruniv.zc.in.
Abstract
AIMS: Aplastic anaemia is a rare disorder characterized by peripheral pancytopenia and hypocellular bone marrow. Recent advancement of miRNA technologies, new promising therapy using small molecule inhibitors was suggested as efficient treatment option. Therefore, the study was undertaken to identify the significantly altered miRNA (miR-1202-upregulation) among aplastic anaemia patients compared to healthy controls by global miRNA expression profiling of bone marrow. MATERIALS AND METHODS: miRNA and gene expression profiles for all the categories of aplastic anaemia patients and healthy controls were generated using Affymetrix probes. KEY FINDINGS: The study was based on freely available miRNA and host gene expression in NCBI GEO dataset. Microarray based gene expression profiling (GSE3807) revealed that RAPGEF5 and MANEA genes were significantly downregulated among aplastic anaemia patients compared to healthy controls and the expression of these genes were again upregulated after application of therapy among those patients compared to pre-therapy condition. RAPGEF5 was involved in Rap1 and Ras signaling pathways those were significantly enriched among aplastic anaemia patients and could be relevant for that phenotype. Microarray based miRNA expression profiling (GSE82095) also identified that miR-1202 was significantly upregulated among aplastic anaemia patients compared to controls and can potentially target RAPGEF5 and MANEA genes based on target prediction of miRNAs. SIGNIFICANCE: Thus synthetic miRNA inhibitors of miR-1202 can be used as a possible therapeutic agent to target miR-1202 and this inhibition can lead to its corresponding target gene upregulation for reversal of disease phenotype.
AIMS: Aplastic anaemia is a rare disorder characterized by peripheral pancytopenia and hypocellular bone marrow. Recent advancement of miRNA technologies, new promising therapy using small molecule inhibitors was suggested as efficient treatment option. Therefore, the study was undertaken to identify the significantly altered miRNA (miR-1202-upregulation) among aplastic anaemiapatients compared to healthy controls by global miRNA expression profiling of bone marrow. MATERIALS AND METHODS: miRNA and gene expression profiles for all the categories of aplastic anaemiapatients and healthy controls were generated using Affymetrix probes. KEY FINDINGS: The study was based on freely available miRNA and host gene expression in NCBI GEO dataset. Microarray based gene expression profiling (GSE3807) revealed that RAPGEF5 and MANEA genes were significantly downregulated among aplastic anaemiapatients compared to healthy controls and the expression of these genes were again upregulated after application of therapy among those patients compared to pre-therapy condition. RAPGEF5 was involved in Rap1 and Ras signaling pathways those were significantly enriched among aplastic anaemiapatients and could be relevant for that phenotype. Microarray based miRNA expression profiling (GSE82095) also identified that miR-1202 was significantly upregulated among aplastic anaemiapatients compared to controls and can potentially target RAPGEF5 and MANEA genes based on target prediction of miRNAs. SIGNIFICANCE: Thus synthetic miRNA inhibitors of miR-1202 can be used as a possible therapeutic agent to target miR-1202 and this inhibition can lead to its corresponding target gene upregulation for reversal of disease phenotype.
Authors: Dan He; Wan Dan; Qing Du; Bing-Bing Shen; Lin Chen; Liang-Zi Fang; Jian-Jun Kuang; Chun-Yu Tang; Ping Cai; Rong Yu; Shui-Han Zhang; Jian-Hua Huang Journal: Drug Des Devel Ther Date: 2022-04-28 Impact factor: 4.319