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

https://doi.org/10.14412/2074-2711-2022-2-64-70

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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.

About the Authors

N. M. Baulina
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Russian Federation

Natalia Mikhailovna Baulina

1, Ostrovityanov St., Moscow 117997, Russia



A. R. Kabaeva
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Russian Federation

1, Ostrovityanov St., Moscow 117997, Russia



A. N. Boyko
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Russian Federation

1, Ostrovityanov St., Moscow 117997, Russia



O. O. Favorova
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Russian Federation

1, Ostrovityanov St., Moscow 117997, Russia



References

1. Walton C, King R, Rechtman L, et al. Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition. Mult Scler. 2020 Dec;26(14):1816-21. doi: 10.1177/1352458520970841. Epub 2020 Nov 11.

2. Mills EA, Mirza A, Mao-Draayer Y. Emerging Approaches for Validating and Managing Multiple Sclerosis Relapse. Front Neurol. 2017 Mar 29;8:116. doi: 10.3389/fneur.2017.00116

3. O'Brien J, Hayder H, Zayed Y, Peng C. Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front Endocrinol (Lausanne). 2018 Aug 3;9:402. doi: 10.3389/fendo.2018.00402

4. Baulina N, Osmak G, Kiselev I, et al. 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 Feb 8;8(2):133. doi: 10.3390/cells8020133

5. Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018 Feb;17(2):162-73. doi: 10.1016/S1474-4422(17)30470-2. Epub 2017 Dec 21.

6. Ebrahimkhani S, Vafaee F, Young PE, et al. Exosomal microRNA signatures in multiple sclerosis reflect disease status. Sci Rep. 2017 Oct 30;7(1):14293. doi: 10.1038/s41598-017-14301-3

7. Jernas M, Malmeström C, Axelsson M, et al. MicroRNA regulate immune pathways in T-cells in multiple sclerosis (MS). BMC Immunol. 2013 Jul 29;14:32. doi: 10.1186/1471-2172-14-32

8. Ingwersen J, Menge T, Wingerath B, et al. Natalizumab restores aberrant miRNA expression profile in multiple sclerosis and reveals a critical role for miR-20b. Ann Clin Transl Neurol. 2015 Jan;2(1):43-55. doi: 10.1002/acn3.152. Epub 2014 Dec 5.

9. Munoz-Culla M, Irizar H, Saenz-Cuesta M, et al. SncRNA (microRNA &snoRNA) opposite expression pattern found in multiple sclerosis relapse and remission is sex dependent. Sci Rep. 2016 Feb 1;6:20126. doi: 10.1038/srep20126

10. Cui C, Yang W, Shi J, et al. Identification and Analysis of Human Sex-biased MicroRNAs. Genomics Proteomics Bioinformatics. 2018 Jun;16(3):200-11. doi: 10.1016/j.gpb.2018.03.004. Epub 2018 Jul 11.

11. Dai R, Ahmed SA. Sexual dimorphism of miRNA expression: a new perspective in understanding the sex bias of autoimmune diseases. Ther Clin Risk Manag. 2014 Mar 3;10:151-63. doi: 10.2147/TCRM.S33517

12. Sharma S, Eghbali M. Influence of sex differences on microRNA gene regulation in disease. Biol Sex Differ. 2014 Feb 1;5(1):3. doi: 10.1186/2042-6410-5-3

13. Song G, Wang L. Transcriptional mechanism for the paired miR-433 and miR-127 genes by nuclear receptors SHP and ERRgamma. Nucleic Acids Res. 2008 Oct;36(18):5727-35. doi: 10.1093/nar/gkn567. Epub 2008 Sep 6.

14. Huan T, Rong J, Liu C, et al. Genome-wide identification of microRNA expression quantitative trait loci. Nat Commun. 2015 Mar 20;6:6601. doi: 10.1038/ncomms7601


Review

For citations:


Baulina N.M., Kabaeva A.R., Boyko A.N., Favorova O.O. Changes in expression of miRNAs from the DLK1-DIO3 locus are characteristic of relapsing-remitting multiple sclerosis regardless of the disease activity. Neurology, Neuropsychiatry, Psychosomatics. 2022;14(2):64-70. (In Russ.) https://doi.org/10.14412/2074-2711-2022-2-64-70

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ISSN 2074-2711 (Print)
ISSN 2310-1342 (Online)