Differential expression of microRNA-7188-5p and miR-7235 regulates Multiple Sclerosis in an experimental mouse model- an Biomarker approach

DOI: https://doi.org/10.21203/rs.3.rs-147349/v1

Abstract

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). First, we used a computational tool to identify a new set of miRNA(s) that are probably implicated in MS. Preliminary, computational screening reveals 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 genes 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, these data suggesting new inflammatory target genes of these promising miRNA biomarkers. The in vivo adoptive transfer model revealed that the suppression of miRNA-7188-5p and miR-7235 changed the pattern of astrocytes and CNSpathophysiology. The current study identified set of miRNAs and their mRNA targets as reciprocal regulator in MS disease. The absence of miRNA-7188-5p and miR-7235 enhanced the disease alleviation. These optimized results highlight new set of miRNA’s based biomarkers with therapeutic potential in experimental MS.

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