Changes in expression of miRNAs from the DLK1-DIO3 locus are characteristic of relapsing-remitting multiple sclerosis regardless of the disease activity

Abstract

The role of miRNAs – small, regulatory, noncoding RNAs – in the multiple sclerosis (MS) development is being intensively investigated. Previously, we the first who observed a significant increase in the expression of 26 microRNA genes localized in the DLK1-DIO3 locus in men with relapsing-remitting MS (RRMS) in peripheral blood mononuclear cells (PBMCs), using RNA sequencing.Objective: to evaluate the possible involvement of miRNAs in the regulation of the activity of the pathological process in RRMS by comparing the miRNA genes expression levels from this locus in patients in remission, relapse, and healthy individuals, separately for men and women.Patients and methods. Analysis of miR-431-5p, miR-127-3p, miR-379, miR-376c, miR-381, miR-410 and miR-656-3p microRNA expression was performed by reverse transcription and subsequent real-time polymerase chain reaction in PBMCs of 16 patients in the relapse stage, 20 patients in remission who did not receive immunomodulatory drugs, and 20 healthy individuals.Results and discussion. The expression levels of all studied miRNAs did not differ in patients in remission and relapse stages, in men and women. At the same time, men (in remission and relapse) showed a significant increase in the levels of all miRNAs compared with healthy men; in women, no changes in expression were observed. A high level of correlation of miRNA expression from the DLK1-DIO3 locus was shown in both patients and healthy individuals from the control group, regardless of gender. Coexpression was observed not only for miRNA genes from the same cluster (14q32.2 or 14q32.31), but also for genes from different clusters.Conclusion. The miRNAs genes from the DLK1-DIO3 locus are involved in the pathophysiology of RMS onset, but not in the processes associated with the transition from remission to relapses. The high consistency of miRNA expression, regardless of the localization of their genes within this region, suggests the presense of a common mechanism that regulates their transcription.