MicroRNA-7188-5p and miR-7235 regulates Multiple sclerosis in an experimental mouse model

小RNA 基因沉默 体内 生物 多发性硬化 癌症研究 疾病 基因 免疫学 医学 病理 遗传学
作者
Hairul-Islam Mohamed Ibrahim,Abdullah M. Alzahrani,Hamza Hanieh,Emad A. Ahmed,Krishnaraj Thirugnanasambantham
出处
期刊:Molecular Immunology [Elsevier BV]
卷期号:139: 157-167 被引量:9
标识
DOI:10.1016/j.molimm.2021.07.002
摘要

The short non-coding microRNAs (miRNAs) have emerged as reliable modulators of various pathological conditions including autoimmune diseases in mammals. The current study, aims to identify new potential differential expressed miRNAs and their downstream mRNA targets of the autoimmune disease, Multiple sclerosis (MS). The study identifies a new set of miRNA(s) that are probably implicated in MS using computational tools. The study further carried-out different in vivo and in vitro experiments to check these identified miRNAs could be role in as therapeutic and prognostic applications. Preliminary insilico screening revealed that miR-659-3p, miR-659-5p, miR-684, miR-3607-3p, miR-3607-5p, miR-3682-3p, miR-3682-5p miR-4647, miR-7188-3p, miR-7188-5p and miR-7235 are specifically elevated in the secondary lymphoid cells of EAE mice. In addition, expression of the downstream target mRNA of these miRNAs such as FXBO33, SGMS-1, ZDHHC-9, GABRA-3, NRXN-2 were reciprocal to miRNA expression in lymphoid cells. These confirmed by applying the mimic and silencing miRNA models, suggesting new inflammatory target genes of these promising miRNA markers. The in vivo adoptive transfer model revealed that the suppression of miRNA-7188-5p and miR-7235 changed the pattern of astrocytes and CNS pathophysiology. The current study opens a new miRNA and their mRNA targets in MS disease. The absence of miRNA-7188-5p and miR-7235 enhanced the disease alleviation, confirms the regulatory effect of these targets. These optimized results highlights new set of miRNA's with therapeutic potential in experimental MS. Further studies are required to confirm these miRNA as therapeutic biomarker.
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