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MicroRNA expression profile in patients in the early stages of ischemic stroke

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Stroke is one of the leading causes of death and disability in the population, has a complex multifactorial nature and develops through the interaction of environmental factors and genetic predisposition, the pattern and mechanisms of which have been insufficiently studied. Ischemic stroke (IS) is most commonly encountered. Objective: to investigate the differential expression of microRNAs (miRNAs) in the plasma of patients in the acute and subacute stages of stroke. Patients and methods. The investigation enrolled 10 patients (5 men and 5 women; mean age, 64.5 years) with IS and 10 gender- and agematched volunteers (a control group). A real-time polymerase chain reaction (PCR) was used to analyze the expression of 45 miRNAs isolated from the plasma samples of the patients on days 1 and 8 after onset of IS and isolated once from those of the controls. Results. A list of 45 miRNAs, that might be potential biomarkers and/or prognostic factors of stroke, was compiled. The investigation showed a decrease in let-7i-3p and miR-23a-3p miRNA expression in patients on the first day after onset of IS compared to the control group. The expression of miR-23a-3p increased in the patients at 8 days after IS. The patients with IS and the controls both showed gender differences in the expression of let-7i-5p and miR-92b-3p. Conclusion. The in-silico analysis revealed specific miRNA clusters associated with the peculiarities of clinical manifestations of IS. This may suggest that the patients with the favorable and unfavorable course of stroke may have its different molecular basis. In addition, it is necessary to take into account gender differences in the expression of individual miRNAs in assessing their significance in the pathogenesis and prognosis of IS.

About the Authors

I. S. Zhanin
I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia, Moscow
Russian Federation

V. A. Gusar
I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia, Moscow
Russian Federation

A. T. Timofeeva
I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia, Moscow
Russian Federation

V. G. Pinelis
I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia, Moscow
Russian Federation

A. Yu. Asanov
I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia, Moscow
Russian Federation


1. WHO. The top 10 causes of death. http: //

2. ICSI. Diagnosis and Initial Treatment of Ischemic Stroke. alog_guidelines/catalog_cardiovascular_guidelines/stroke/

3. ISW Party. National clinical guideline for stroke. SupportFiles/Documents/Guidelines/2016-National-Clinical-Guideline-for-Stroke-5t-(1).aspx

4. VanGilder RL, Rosen CL, Barr TL, et al. Targeting the neurovascular unit for treatment of neurological disorders. Pharmacol Ther. 2011 Jun;130(3):239-47. doi: 10.1016/j.pharmthera. 2010.12.004. Epub 2010 Dec 21.

5. Sepramaniam S, Tan JR, Tan KS, et al. Circulating microRNAs as biomarkers of acute stroke. Int J Mol Sci. 2014 Jan 20;15(1):1418-32. doi: 10.3390/ijms15011418.

6. Choi KS, Kim HJ, Chun HJ, et al. Prognostic role of copeptin after stroke: A systematic review and meta-analysis of observational studies. Sci Rep. 2015 Jun 29;5:11665. doi: 10.1038/srep11665.

7. Jickling GC, Sharp FR. Blood biomarkers of ischemic stroke. Neurotherapeutics. 2011 Jul;8(3): 349-60. doi: 10.1007/s13311-011-0050-4.

8. Mick E, Shah R, Tanriverdi K, et al. Stroke and Circulating Extracellular RNAs. Stroke. 2017 Apr;48(4):828-834. doi: 10.1161/ STROKEAHA.116.015140. Epub 2017 Mar 13.

9. Valinezhad Orang A, Safaralizadeh R, Kazemzadeh-Bavili M. Mechanisms of miRNA-Mediated Gene Regulation from Common Downregulation to mRNA-Specific Upregulation. Int J Genomics. 2014;2014: 970607. doi: 10.1155/2014/970607. Epub 2014 Aug 10.

10. 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. eCollection 2014.

11. Pandey AC, Semon JA, Kaushal D, et al. MicroRNA profiling reveals age-dependent differential expression of nuclear factor B and mitogen-activated protein kinase in adipose and bone marrow-derived human mesenchymal stem cells. Stem Cell Res Ther. 2011 Nov 14;2(6):49. doi: 10.1186/scrt90.

12. Ding Y, Yan JL, Fang AN, et al. Circulating miRNAs as novel diagnostic biomarkers in hepatocellular carcinoma detection: a metaanalysis based on 24 articles. Oncotarget. 2017 Jul 4;8(39):66402-66413. doi: 10.18632/oncotarget.18949. eCollection 2017 Sep 12.

13. Sempere L, Keto J, Fabbri M. Exosomal MicroRNAs in Breast Cancer towards Diagnostic and Therapeutic Applications. Cancers (Basel). 2017 Jun 24;9(7). pii: E71. doi: 10.3390/cancers9070071.

14. Ouyang YB, Lu Y, Yue S, et al. miR-181 regulates GRP78 and influences outcome from cerebral ischemia in vitro and in vivo. Neurobiol Dis. 2012 Jan;45(1):555-63. doi: 10.1016/j.nbd. 2011.09.012. Epub 2011 Sep 24.

15. Liu C, Zhao L, Han S, et al. Identification and functional analysis of microRNAs in mice following focal cerebral ischemia injury. Int J Mol Sci. 2015 Oct 14;16(10):24302-18. doi: 10.3390/ijms161024302.

16. Xu LJ, Ouyang YB, Xiong X, et al. Post-stroke treatment with miR-181 antagomir reduces injury and improves long-term behavioral recovery in mice after focal cerebral ischemia. Exp Neurol. 2015 Feb;264:1-7.

17. doi: 10.1016/j.expneurol.2014.11.007. Epub 2014 Nov 26.

18. Scherrer N, Fays F, Mueller B, et al. MicroRNA 150-5p Improves Risk Classification for Mortality within 90 Days after Acute Ischemic Stroke. J Stroke. 2017 Sep;19(3): 323-332. doi: 10.5853/jos.2017.00423. Epub 2017 Sep 29.

19. Allen LM, Hasso AN, Handwerker J, et al. Sequence-specific MR Imaging Findings That Are Useful in Dating Ischemic Stroke. Radiographics. 2012 Sep-Oct;32(5):1285-97; discussion 1297-9. doi: 10.1148/rg.325115760.

20. NIND. NIH Stroke Scale. https://www.ninds.

21. Гусар В, Тимофеева А, Жанин И и др. Оценка временных паттернов экспрессии микроРНК в ткани головного мозга, плазме и лейкоцитах крови крыс. Молекулярная биология. 2017;51(4):683–95. [Gusar V, Timofeeva A, Zhanin I, et al. Evaluation of temporal patterns of MicroRNA expression in brain tissue, plasma and leukocytes of rat blood. Molekulyarnaya biologiya. 2017;51(4):683–95. (In Russ.)].

22. Dweep H, Gretz N. miRWalk2.0: a comprehensive atlas of microRNA-target interactions. Nat Methods. 2015 Aug;12(8):697. doi: 10.1038/ nmeth.3485.

23. Kozomara A, Griffiths-Jones S. miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 2014 Jan;42(Database issue):D68-73. doi: 10.1093/nar/gkt1181. Epub 2013 Nov 25.

24. Marabita F, de Candia P, Torri A, et al. Normalization of circulating microRNA expression data obtained by quantitative realtime RT-PCR. Brief Bioinform. 2016 Mar;17(2): 204-12. doi: 10.1093/bib/bbv056. Epub 2015 Aug 3.

25. Vandesompele J, De Paepe A, Speleman F, et al. Elimination of Primer–Dimer Artifacts and Genomic Coamplification Using a Two-Step SYBR Green I Real-Time RT-PCR. Anal Biochem. 2002 Apr 1;303(1):95-8.

26. Andersen CL, Jensen JL, Orntoft TF. Normalization of Real-Time Quantitative Reverse Transcription-PCR Data: A Model-Based Variance Estimation Approach to Identify Genes Suited for Normalization, Applied to Bladder and Colon Cancer Data Sets. Cancer Res. 2004 Aug 1;64(15):5245-50.

27. Zhou J, Zhang J. Identification of miRNA-21 and miRNA-24 in plasma as potential early stage markers of acute cerebral infarction. Mol Med Rep. 2014 Aug;10(2):971-6. doi: 10.3892/ mmr.2014.2245. Epub 2014 May 16.

28. Qureshi R, Sacan A. A novel method for the normalization of microRNA RT-PCR data. BMC Med Genomics. 2013;6 Suppl 1:S14. doi: 10.1186/1755-8794-6-S1-S14. Epub 2013 Jan 23.

29. Urbich C, Kuehbacher A, Dimmeler S. Role of microRNAs in vascular diseases, inflammation, and angiogenesis. Cardiovasc Res. 2008 Sep 1;79(4):581-8. doi: 10.1093/ cvr/cvn156. Epub 2008 Jun 11.

30. Chen X, Ba Y, Ma L, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008 Oct;18(10):997-1006. doi: 10.1038/cr.2008.282.

31. Chen Y, Gao C, Sun Q, et al. MicroRNA-4639 Is a Regulator of DJ-1 Expression and a Potential Early Diagnostic Marker for Parkinson’s Disease. Front Aging Neurosci. 2017 Jul 21;9:232. doi: 10.3389/ fnagi.2017.00232. eCollection 2017.

32. Jickling GC, Ander BP, Shroff N, et al. Leukocyte response is regulated by microRNA let7i in patients with acute ischemic stroke. Neurology. 2016 Nov 22;87(21): 2198-2205. Epub 2016 Oct 26.

33. Rao YS, Mott NN, Wang Y, et al. MicroRNAs in the aging female brain: a putative mechanism for age-specific estrogen effects. Eur J Neurosci. 2016 Nov;44(10):2795-2806. doi: 10.1111/ejn.13377. Epub 2016 Sep 14.

34. Zhao H, Tao Z, Wang R, et al. MicroRNA-23a-3p attenuates oxidative stress injury in a mouse model of focal cerebral ischemia-reperfusion. Brain Res. 2014 Dec 10; 1592:65-72. doi: 10.1016/j.brainres.2014.09.055. Epub 2014 Oct 2.

35. Maciejak A, Kiliszek M, Opolski G, et al. miR-22-5p revealed as a potential biomarker involved in the acute phase of myocardial infarction via profiling of circulating microRNAs. Mol Med Rep. 2016 Sep;14(3):2867-75. doi: 10.3892/mmr.2016. 5566. Epub 2016 Jul 27.

36. Jovicic A, Zaldivar Jolissaint JF, Moser R, et al. MicroRNA-22 (miR-22) overexpression is neuroprotective via general anti-apoptotic effects and may also target specific Huntington’s disease-related mechanisms. PLoS One. 2013;8(1):e54222. doi: 10.1371/journal.pone.0054222. Epub 2013 Jan 17.

37. Chen Z, Qi Y, Gao C. Cardiac myocyteprotective effect of microRNA-22 during ischemia and reperfusion through disrupting the caveolin-3/eNOS signaling. Int J Clin Exp Pathol. 2015 May 1;8(5):4614-26. eCollection 2015.

38. Long M, Zhan M, Xu S, et al. miR-92b-3p acts as a tumor suppressor by targeting Gabra3 in pancreatic cancer. Mol Cancer. 2017 Oct 27; 16(1):167. doi: 10.1186/s12943-017-0723-7.

39. Paik NJ, Yang E. Role of GABA plasticity in stroke recovery. Neural Regen Res. 2014 Dec 1; 9(23):2026-8. doi: 10.4103/1673-5374.147920.

40. Blicher JU, Near J, Naess-Schmidt E, et al. GABA levels are decreased after stroke and GABA changes during rehabilitation correlate with motor improvement. Neurorehabil Neural Repair. 2015 Mar-Apr;29(3):278-86. doi: 10.1177/1545968314543652. Epub 2014 Jul 22.

For citation:

Zhanin I.S., Gusar V.A., Timofeeva A.T., Pinelis V.G., Asanov A.Yu. MicroRNA expression profile in patients in the early stages of ischemic stroke. Neurology, Neuropsychiatry, Psychosomatics. 2018;10(3):72-78. (In Russ.)

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