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MicroRNA-7188-5p and miR-7235 regulates Multiple sclerosis in an experimental mouse model
Molecular Immunology ( IF 3.2 ) Pub Date : 2021-09-17 , DOI: 10.1016/j.molimm.2021.07.002
Hairul-Islam Mohamed Ibrahim 1 , Abdullah AlZahrani 2 , Hamza Hanieh 3 , Emad A Ahmed 4 , Krishnaraj Thirugnanasambantham 5
Affiliation  

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.



中文翻译:

MicroRNA-7188-5p 和 miR-7235 在实验小鼠模型中调节多发性硬化症

短的非编码微 RNA (miRNA) 已成为各种病理状况的可靠调节剂,包括哺乳动物的自身免疫性疾病。目前的研究旨在确定自身免疫性疾病多发性硬化症 (MS) 的新潜在差异表达 miRNA 及其下游 mRNA 靶标。该研究使用计算工具确定了一组可能与 MS 相关的新 miRNA。该研究进一步进行出不同的体内体外检查这些鉴定出的 miRNA 的实验可能在治疗和预后应用中发挥作用。初步的计算机筛选显示 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 和 miR-7235 在 EAE 小鼠的次级淋巴细胞中特异性升高。此外,FXBO33、SGMS-1、ZDHHC-9、GABRA-3、NRXN-2等miRNA下游靶mRNA的表达与淋巴细胞中miRNA的表达呈倒数关系。这些通过应用模拟和沉默 miRNA 模型得到证实,表明这些有前途的 miRNA 标记物的新炎症靶基因。在体内过继转移模型显示抑制 miRNA-7188-5p 和 miR-7235 改变了星形胶质细胞的模式和 CNS 病理生理学。目前的研究开辟了一个新的 miRNA 及其在 MS 疾病中的 mRNA 靶点。miRNA-7188-5p 和 miR-7235 的缺失增强了疾病的缓解,证实了这些靶标的调节作用。这些优化的结果突出了在实验性 MS 中具有治疗潜力的一组新 miRNA。需要进一步的研究来确认这些 miRNA 作为治疗生物标志物。

更新日期:2021-09-19
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