A role of microRNA in the pathogenesis of ischemic stroke

Novikova L.B.; Minibaeva G.M.

doi:https://doi.org/10.17116/jnevro20181183243-47

Close metadata

Recommended articles:

Early antithrombotic protection of the brain in patients with ischemic stroke. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(8-2):5-10

Results of the implementation of reperfusion technologies in ischemic stroke. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(8-2):32-39

Results of the international multicenter randomized, double-blind, placebo-controlled clinical trial for the evaluation of the efficacy and safety of the sequential therapy with ethylmethylhydroxypyridine succinate in patients in the acute and early recovery periods of ischemic stroke (MIR). S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(8-2):40-53

Mathematical modeling of outcomes in patients with clinical combination of ischemic stroke and COVID-19 complicated by multiple organ failure. Russian Journal of Anesthesiology and Reanimatology. 2025;(3):42-49

Socio-economic damage caused by elevated low-density lipoprotein cholesterol levels. Medical Technologies. Assessment and Choice. 2025;(2):88-98

Diagnostic strategies for post-COVID syndrome. Russian Journal of Preventive Medicine. 2025;(6):126-130

Cerebrolysin with reperfusion therapy in ischemic stroke: a prospective analysis of multimodal brain imaging data from the CEREHETIS trial. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(6):84-98

Prediction of mortality in severe ischemic stroke during COVID-19 in patients with multiorgan dysfunction. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(6):120-127

Spectral analysis in metabolomics of skin neoplasms. Russian Journal of Clinical Dermatology and Venereology. 2025;(3):277-283

A clinical case of treating a patient with severe ischemic stroke and cancer. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(8):114-117

Abstract:

Ischemic stroke (IS) is one of the leading causes of death and disability worldwide. Among all the causes of IS, cardioembolic stroke (CEI) accounts for up to 40%. Based on the literature data, modern ideas about the role and location of cardiac diseases in the pathogenesis of CEI are presented. The leading cause of CEE is non-rheumatic atrial fibrillation. Numerous attempts to study and prove the genetic nature of the development of IS led to the discovery of new markers — micribonucleic acids (microRNAs), the regulators of gene expression, that inhibit mRNA translation and play a key role in the pathogenesis of IS. This review summarizes the current knowledge of microRNAs, their ability to simultaneously regulate several target genes, and their significance as potential diagnostic and prognostic biomarkers in IS.

Keywords:

ischemic stroke

cardioembolic stroke

microRNA

biomarkers

Authors:

Novikova L.B.

Bol'nitsa skoroĭ meditsinskoĭ pomoshchi, Ufa

Minibaeva G.M.

Bashkir State Medical University, Ufa, Russia

Close metadata

References:

Suslina ZA, Varakin YuYa, Vereshhagin NV. Sosudisty`e zabolevaniya golovnogo mozga. M.: MEDpress-inform; 2009. (In Russ.)
Gusev EI, Skvorczova VI, Stahovskaya LV. Problemy` insul`ta v Rossijskoj Federacii: vremya aktivny`x dejstvij. Zhurnal Nevrologii i Psihiatrii im. S.S. Korsakova. 2007;107:8:4-10. (In Russ.)
Geraskina LA. Kardioe`mbolicheskij insul`t: mnogoobrazie prichin i sovremenny`e podxody` k profilaktike. Nevrologiya, nejropsihiatriya, psihosomatika. 2013;(4):60-65. (In Russ.)
Kotova OV, Akarachkova ES. Gipertenzivnaya ehncefalopatiya: patogenez i obshchie principy profilaktiki. Farmateka. 2010;12(206):66-71. (In Russ.)
Mediko-demograficheskie pokazateli zdorov’ya naseleniya. Gosudarstvennyj doklad o sostoyanii zdorov’ya naseleniya Rossijskoj Federacii v 2005 g. Zdravoohranenie RF. 2007;5(1):8-18. (In Russ.)
Parfenov VA, Gurak SV. Povtornyj ishemicheskij insul’t i ego profilaktika u bol’nyh s arterial’noj gipertoniej. Zhurnal Nevrologii i Psihiatrii im. S.S. Korsakova (Insul’t). 2005;105:14:3-7. (In Russ.)
Law M, Wald N, Morris J. Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy. Health Technol Assess. 2003;7:1-94.
Hoogen van den P. The relation between blood pressure and mortality due to coronary heart dis-ease among men in different parts of the world. N Engl J Med. 2000;342:1-8.
Fonyakin AV, Suslina ZA, Geraskina LA. Kardiologicheskaya diagnostika pri ishemicheskom insul’te. SPb.: INKART; 2005. (In Russ.)
Petty GW, Brown RD, Whisnant JP. Ischemic stroke subtypes. A population — based study of functional outcome, survival and recurrence. Stroke. 2000;31:1062-1068.
Urbinelli R, Bolard P, Lemesle M. Stroke patterns in cardio-embolic infarction in a population-based study. Neurol Res. 2001;23:309-314.
Suslina ZA, Fonyakin AV. Prakticheskaya kardionevrologiya. M.: IMA-PRESS; 2010. (In Russ.)
Trunova ES, Samohvalova EV, Geraskina LA, Fonyakin AV. Ishemicheskij insul’t: sostoyanie serdca i techenie postinsul’tnogo perioda. Klinicheskaya farmakologiya i terapiya. 2007;5:55-58. (In Russ.)
Fonyakin AV, Geraskina LA. Profilaktika ishemicheskogo insul’ta. Rekomendacii po antitromboticheskoj terapii. Pod red. Suslinoj Z.A. M.: IMA-PRESS; 2014. (In Russ.)
Geraskina LA. Kardioehmbolicheskij insul’t: mnogoobrazie prichin i sovremennye podhody k profilaktike. Nevrologiya, nejropsihiatriya, psihosomatika. 2013;(4):60-65. (In Russ.) https://doi.org/10.14412/2074-2711-2013-2457
Andreeva TV, Kunizheva SS. Analiz regulyatornyh RNK, svyazannyh s razvitiem boleznej mozga. Metodicheskoe posobie k praktikumu «Genetika povedeniya kognitivnyh sposobnostej. Norma i patologiya». M.: Cifrovichok; 2012. (In Russ.)
John B, Enright AJ, Aravin A. Human MicroRNA Targets. PLoS Biol. 2004;2(11):1862-1879. https://doi.org/10.1371/journal.pbio.0020363
Mishra PJ, Bertino JR. MicroRNA polymorphisms: the future of pharmacogenomics, molecular epidemiology and individualized medicine. Pharmacogenomics. 2009;10(3):399-416. https://doi.org/10.2217/14622416.10.3.399
Chen L, Lim SH, Yeh Y. Role of microRNAs in atherosclerosis and restenosis. J of Biomed Sci. 2012;19(79). https://doi.org/10.1186/1423-0127-19-79
Shah AA, Meese E, Blin N. Profiling of regulatory microRNA transcriptomes in various biological processes: a review. J Appl Genet. 2010;51(4):501-507. https://doi.org/10.1007/BF03208880
Alexiou P, Vergoulis T, Gleditzsch M, Prekas G, Dalamagas T, Megraw M, Grosse I, Sellis T, Hatzigeorgiou AG. MiRGen 2.0: a database of microRNA genomic information and regulation. Nucleic Acids Research. 2010;38:137-141. https://doi.org/10.1093/nar/gkp888
John B. Human MicroRNA. PLoS Biol. 2004;2(11):1862-1879. https://doi.org/10.1371/journal.pbio.0040763
Thum T. MicroRNA therapeutics in cardiovascular medicine. EMBO Mol Med. 2011;4:3-14. https://doi.org/10.1002/emmm.201100191
Zhang BK, Lai X, Jia SJ. Epigenetics in atherosclerosis: a clinical perspective. Discov Med. 2015;19(103):73-80.
Ambros V. MicroRNAs Tiny Regulators with Great Potential. Cell. 2001;107:823-826.
Shah AA. Profiling of regulatory microRNA transcriptomes in various biological processes: a review. J Appl Genet. 2014;43(3):312-316. https://doi.org/10.1007/BF03258932
Silvestre-Roig C, Winther MP, Weber C. Atherosclerosis Plaque Destabilization: Mechanism, Models, and Therapeutic Strategies. Circ Res. 2014;114:214-226.
Sonkoly E, Pivarcsi A. Advances in microRNAs: implications for immunity and inflammatory diseases. J Cell Mol Med. 2009;13:24-38. https://doi.org/10.1111/j.1582-4934.2008.00534.x
Xu J, Zhu X, Wu L, Yang R, Yang Z, Wang Q, Wu F. MicroRNA-122 suppresses cell proliferation and induces cell apoptosis in hepatocellular carcinoma by directly targeting Wnt/beta-catenin pathway. Liver Int. 2012;32:752-760. https://doi.org/10.1111/j.1478-3231.2011.02750.x
Dumortier O, Van Obberghen E. MicroRNAs in pancreas development. Diabetes Obes Metab. 2012;14(3):22-28. https://doi.org/10.1111/j.1463-1326.2012.01656.x
Hinton A, Hunter S, Reyes G. From pluripotency to islets: miRNAs as critical regulators of human cellular differentiation. Adv Genet. 2012;79:1-34. https://doi.org/10.1016/B978-0-12-394395-8.00001-3
Ouyang L, Shi Z, Zhao S. Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis. Cell Prolif. 2012;45:487-498. https://doi.org/10.1111/j.1365-2184.2012.00845.x
Ambros V. The functions of animal microRNAs. Nature. 2004;431:350-355.
Khoshnam SE, Winlow W, Farbood Y, Moghaddam HF, Farzaneh M. Emerging Roles of microRNAs in Ischemic Stroke: As Possible Therapeutic Agents. J of Stroke. 2017;19(2):166-187. https://doi.org/10.5853/jos.2016.01368
Yin KJ, Hamblin M, Chen YE. Angiogenesis-regulating microRNAs and ischemic stroke. Curr Vasc Pharmacol. 2015;13(3):352-365.
Chen Y, Song Y, Huang J, Qu M, Zhang Y, Geng J, Zhang Z, Liu J, Yang GY. Increased Circulating Exosomal miRNA-223 Is Associated with Acute Ischemic Stroke. Front Neurol. 2017;8:57. https://doi.org/10.3389/fneur.2017.00057
Yao S, Tang B, Li G, Fan R, Cao F. MiR-455 inhibits neuronal cell death by targeting TRAF3 in cerebral ischemic stroke. Neuropsychiatric Dis Treat. 2016;12:3083-3092.
Murphy TH, Li P, Betts K, Liu R. Two-photon imaging of stroke onset in vivo reveals that NMDA-receptor independent ischemic depolarization is the major cause of rapid reversible damage to dendrites and spines. J Neurosci. 2008;28:1756-1772. https://doi.org/10.1523/JNEUROSCI.5128-07.2008
Baron JC. Mapping the ischaemic penumbra with PET: impli¬cations for acute stroke treatment. Cerebrovasc Dis. 1999;9:193-201.
Jung S, Gilgen M, Slotboom J, El-Koussy M, Zubler C, Kiefer C. Factors that determine penumbral tissue loss in acute ischaemic stroke. Brain. 2013;136(12):3554-3560. https://doi.org/10.1093/brain/awt246
Kulshreshtha R, Ferracin M, Negrini M, Calin GA, Davuluri RV, Ivan M. Regulation of microRNA expression: the hypoxic component. Cell Cycle. 2007;6(12):1426-1431.
Kulshreshtha R, Ferracin M, Wojcik SE. A microRNA signature of hypoxia. Mol Cell Biol. 2007;27(5):1859-1867. https://doi.org/10.1128/MCB.01395-06
Crosby ME, Devlin CM, Glazer PM, Calin GA, Ivan M. Emerging roles of microRNAs in the molecular responses to hypoxia. Curr Pharm Des. 2009;15(33):3861-3866.
Crosby ME, Kulshreshtha R, Ivan M, Glazer PM. MicroRNA regulation of DNA repair gene expression in hypoxic stress. Cancer Res. 2009;69(3):1221-1229. https://doi.org/10.1158/0008-5472.CAN-08-2516
Fasanaro P, Greco S, Ivan M, Capogrossi MC, Martelli F. microRNA: emerging therapeutic targets in acute ischemic diseases. Pharmacol Ther. 2010;125(1):92-104. https://doi.org/10.1016/j.pharmthera.2009.10.003
Harraz MM, Eacker SM, Wang X, Dawson TM, Dawson VL. MicroRNA-223 is neuroprotective by targeting glutamate receptors. Proc Natl Acad Sci USA. 2012;109:18962-18967. https://doi.org/10.1073/pnas.1121288109
Li SH, Su SY, Liu JL. Differential Regulation of microRNAs in Patients with Ischemic Stroke. Curr Neurovasc Res. 2015;12(3):214-221.
Zhou X, Su S, Li S, Pang X, Chen C, Li J, Liu J. MicroRNA-146a down-regulation correlates with neuroprotection and targets pro-apoptotic genes in cerebral ischemic injury in vitro. Brain Res. 2016;1648(A):136-143. https://doi.org/10.1016/j.brainres.2016.07.034
Dharap A, Bowen K, Place R, Li LC, Vemuganti R. Transient focal ischemia induces extensive temporal changes in rat cerebral microRNAome. J Cereb Blood Flow Metab. 2009;29:675-687. https://doi.org/10.1038/jcbfm.2008.157
Iyer A, Zurolo E, Prabowo A, Fluiter K, Spliet WG, van Rijen PC. MicroRNA-146a: a key regulator of astrocyte-mediated inflammatory response. PLoS One. 2012;7:44789. https://doi.org/10.1371/journal.pone.0044789
Chol H, Ko KH, Kim JO, Kim J, Oh SH, Han IB, Cho KG, Kim OJ, Nam KK. Association of miR-34a, miR-130a, miR-150 and miR-155 polymorphisms with the risk of ischemic stroke. Int J Mol Med. 2016;38:345-356. https://doi.org/10.3892/ijmm.2016.2609
Ni J, Wang X, Chen S, Liu H, Wang Y, Xu X, Cheng J, Jia J, Zhen X. MicroRNA let-7c-5p protects against cerebral ischemia injury via mechanisms involving the inhibition of microglia activation. Brain Behavior Immun. 2015;49:75-85. https://doi.org/10.1016/j.bbi.2015.04.014
Ni J, Wang X, Chen S, Liu H, Wang Y, Xu X. MicroRNA let-7c-5p protects against cerebral ischemia injury via mechanisms involving the inhibition of microglia activation. Brain Behav Immun. 2015;49:75-85. https://doi.org/10.1016/j.bbi.2015.04.014
Tan JR, Tan KS, Yong FL, Armugam A, Wang CW, Jeyaseelan K. MicroRNAs regulating cluster of differentiation 46 (CD46) in cardioembolic and non-cardioembolic stroke. PLoS ONE. 201712(2):0172131. https://doi.org/10.1371/journal.pone.0172131