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Cells 2019, 8(2), 133; https://doi.org/10.3390/cells8020133

MiRNAs from DLK1-DIO3 Imprinted Locus at 14q32 are Associated with Multiple Sclerosis: Gender-Specific Expression and Regulation of Receptor Tyrosine Kinases Signaling

Pirogov Russian National Research Medical University, Moscow 117997, Russia
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Received: 10 January 2019 / Revised: 1 February 2019 / Accepted: 7 February 2019 / Published: 8 February 2019
(This article belongs to the Special Issue The Molecular and Cellular Basis for Multiple Sclerosis)
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Abstract

Relapsing-remitting multiple sclerosis (RRMS) is the most prevalent course of multiple sclerosis. It is an autoimmune inflammatory disease of the central nervous system. To investigate the gender-specific involvement of microRNAs (miRNAs) in RRMS pathogenesis, we compared miRNA profiles in peripheral blood mononuclear cells separately in men and women (eight RRMS patients versus four healthy controls of each gender) using high-throughput sequencing. In contrast to women, six downregulated and 26 upregulated miRNAs (padj < 0.05) were identified in men with RRMS. Genes encoding upregulated miRNAs are co-localized in DLK1-DIO3 imprinted locus on human chromosome 14q32. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis was performed in independent groups of men (16 RRMS patients and 10 healthy controls) and women (20 RRMS patients and 10 healthy controls). Increased expression of miR-431, miR-127-3p, miR-379, miR-376c, miR-381, miR-410 and miR-656 was again demonstrated in male (padj < 0.05), but not in female RRMS patients. At the same time, the expression levels of these miRNAs were lower in healthy men than in healthy women, whereas in RRMS men they increased and reached or exceeded levels in RRMS women. In general, we demonstrated that expression levels of these miRNAs depend both on “health–disease” status and gender. Network-based enrichment analysis identified that receptor tyrosine kinases-activated pathways were enriched with products of genes targeted by miRNAs from DLK1-DIO3 locus. These results suggest the male-specific involvement of these miRNAs in RRMS pathogenesis via regulation of PI3K/Akt signaling. View Full-Text
Keywords: relapsing-remitting multiple sclerosis; miRNA; DLK1-DIO3 imprinted locus; gender specificity; network-based enrichment analysis; receptor tyrosine kinase relapsing-remitting multiple sclerosis; miRNA; DLK1-DIO3 imprinted locus; gender specificity; network-based enrichment analysis; receptor tyrosine kinase
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Baulina, N.; Osmak, G.; Kiselev, I.; Popova, E.; Boyko, A.; Kulakova, O.; Favorova, O. MiRNAs from DLK1-DIO3 Imprinted Locus at 14q32 are Associated with Multiple Sclerosis: Gender-Specific Expression and Regulation of Receptor Tyrosine Kinases Signaling. Cells 2019, 8, 133.

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