Skip to main content

Advertisement

SpringerLink
Log in

MicroRNAs Expression and Function in Cerebral Ischemia Reperfusion Injury

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

MicroRNAs (miRNAs) are small (18 ~ 25 nt) noncoding single-stranded RNA molecules that act as negative regulators of gene expression and modulating the stability and/or the translational efficiency of target messenger RNAs. Studies have shown that miRNAs control diverse aspects of brain disease. Recently, several studies have suggested that miRNAs alter the response to ischemia reperfusion injury and regulate the expression of various key elements in cell survival and apoptosis. This review article gives a brief overview of some miRNAs (miR-15a/b, miR-21, miR-29b/c, miR-124, miR-145, miR-181, miR-200 family, miR-338, miR-422a, miR-497, and miR let 7 family) in cerebral ischemia reperfusion injury. Although miRNAs could be potential therapeutic targets for the treatment of ischemia reperfusion injury, their safety and other limitations need further confirmation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ (2011) Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 29:341–345

    Article  CAS  PubMed  Google Scholar 

  • Baranova O, Miranda L, Pichiule P, Dragatsis I, Johnson R, Chavez J (2007) Neuron-specific inactivation of the hypoxia inducible factor 1 alpha increases brain injury in a mouse model of transient focal cerebral ischemia. J Neurosci 27:6320–6332

    Article  CAS  PubMed  Google Scholar 

  • Bergamaschi D, Samuels Y, O'Neil N, Trigiante G, Crook T, Hsieh J, O'Connor D, Zhong S, Campargue I, Tomlinson M, Kuwabara P, Lu X (2003) iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human. Nat Genet 33:162–167

    Article  CAS  PubMed  Google Scholar 

  • Bhalala OG, Srikanth M, Kessler JA (2013) The emerging roles of microRNAs in CNS injuries. Nat Rev Neurol 9:328–339

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Buller B, Liu X, Wang X, Zhang R, Zhang L, Hozeska-Solgot A, Chopp M, Zhang Z (2010) MicroRNA-21 protects neurons from ischemic death. FEBS J 277:4299–4307

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chen X, Gong J, Zeng H, Chen N, Huang R, Huang Y, Nie L, Xu M, Xia J, Zhao F, Meng W, Zhou Q (2010) MicroRNA145 targets BNIP3 and suppresses prostate cancer progression. Cancer Res 70:2728–2738

    Article  CAS  PubMed  Google Scholar 

  • Deng X, Zhong Y, Gu L, Shen W, Guo J (2013) MiR-21 involve in ERK-mediated upregulation of MMP9 in the rat hippocampus following cerebral ischemia. Brain Res Bull 94:56–62

    Article  CAS  PubMed  Google Scholar 

  • Dharap A, Bowen K, Place R, Li L, Vemuganti R (2009) Transient focal ischemia induces extensive temporal changes in rat cerebral microRNAome. J Cereb Blood Flow Metab 29:675–687

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Doeppner TR, Doehring M, Bretschneider E, Zechariah A, Kaltwasser B, Muller B, Koch JC, Bahr M, Hermann DM, Michel U (2013) MicroRNA-124 protects against focal cerebral ischemia via mechanisms involving Usp14-dependent REST degradation. Acta Neuropathol

  • Fagan A, Perrin R (2012) Upcoming candidate cerebrospinal fluid biomarkers of Alzheimer's disease. Biomark Med 6:455–476

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Foust KD, Nurre E, Montgomery CL, Hernandez A, Chan CM, Kaspar BK (2009) Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat Biotechnol 27:59–65

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Han J, Lee Y, Yeom K, Kim Y, Jin H, Kim V (2004) The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev 18:3016–3027

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • He Q, Peng G, Liu W, Luo B (2010) Interaction of microRNA-338 and its potential targeting protein eiF4E3. Zhejiang Da Xue Xue Bao Yi Xue Ban 39:583–588

    CAS  PubMed  Google Scholar 

  • Head B, Patel P (2007) Anesthetics and brain protection. Curr Opin Anaesthesiol 20:395–399

    Article  PubMed  Google Scholar 

  • Higashida R, Furlan A, Roberts H, Tomsick T, Connors B, Barr J, Dillon W, Warach S, Broderick J, Tilley B, Sacks D (2003) Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke. Stroke 34:e109–e137

    Article  PubMed  Google Scholar 

  • Hunsberger JG, Fessler EB, Wang Z, Elkahloun AG, Chuang DM (2012) Post-insult valproic acid-regulated microRNAs: potential targets for cerebral ischemia. Am J Transl Res 4:316–332

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hutvágner G, McLachlan J, Pasquinelli A, Bálint E, Tuschl T, Zamore P (2001) A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science 293:834–838

    Article  PubMed  Google Scholar 

  • Janssen HL, Reesink HW, Lawitz EJ, Zeuzem S, Rodriguez-Torres M, Patel K, van der Meer AJ, Patick AK, Chen A, Zhou Y, Persson R, King BD, Kauppinen S, Levin AA, Hodges MR (2013) Treatment of HCV infection by targeting microRNA. The Engl J Med 368:1685–1694

    Article  CAS  Google Scholar 

  • Jeyaseelan K, Lim K, Armugam A (2008) MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion. Stroke 39:959–966

    Article  CAS  PubMed  Google Scholar 

  • Judge AD, Sood V, Shaw JR, Fang D, McClintock K, MacLachlan I (2005) Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA. Nat Biotechnol 23:457–462

    Article  CAS  PubMed  Google Scholar 

  • Katakowski M, Buller B, Zheng X, Lu Y, Rogers T, Osobamiro O, Shu W, Jiang F, Chopp M (2013) Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth. Cancer Lett 335:201–204

    Article  CAS  PubMed  Google Scholar 

  • Lages E, Ipas H, Guttin A, Nesr H, Berger F, Issartel J (2012) MicroRNAs: molecular features and role in cancer. Front Biosci 17:2508–2540

    Article  Google Scholar 

  • Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Rådmark O, Kim S, Kim V (2003) The nuclear RNase III Drosha initiates microRNA processing. Nature 425:415–419

    Article  CAS  PubMed  Google Scholar 

  • Lee Y, Kim M, Han J, Yeom K, Lee S, Baek S, Kim V (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23:4051–4060

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lee S, Chu K, Jung K, Yoon H, Jeon D, Kang K, Park K, Bae E, Kim M, Lee S, Roh J (2010) MicroRNAs induced during ischemic preconditioning. Stroke 41:1646–1651

    Article  PubMed  Google Scholar 

  • Lee ST, Chu K, Jung KH, Kim JH, Huh JY, Yoon H, Park DK, Lim JY, Kim JM, Jeon D, Ryu H, Lee SK, Kim M, Roh JK (2012) miR-206 regulates brain-derived neurotrophic factor in Alzheimer disease model. Ann Neurol 72:269–277

    Article  CAS  PubMed  Google Scholar 

  • Li Z, Li T, Wang F, Liu S, Liu Y, Liu X, Zhuang X (2009) MicroRNA alteration after H2O2-induced PC12 cells apoptosis and regulatory mechanism of bcl-w. J Sun Yat-Sen Univ 30:34–40

    Google Scholar 

  • Li R, Yan G, Li Q, Sun H, Hu Y, Sun J, Xu B (2012) MicroRNA-145 protects cardiomyocytes against hydrogen peroxide (H2O2)-induced apoptosis through targeting the mitochondria apoptotic pathway. PLoS One 7:e44907

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lin Y, Liu X, Cheng Y, Yang J, Huo Y, Zhang C (2009) Involvement of MicroRNAs in hydrogen peroxide-mediated gene regulation and cellular injury response in vascular smooth muscle cells. J Biol Chem 284:7903–7913

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Liu D, Tian Y, Ander B, Xu H, Stamova B, Zhan X, Turner R, Jickling G, Sharp F (2010) Brain and blood microRNA expression profiling of ischemic stroke, intracerebral hemorrhage, and kainate seizures. J Cereb Blood Flow Metab 30:92–101

    Article  PubMed Central  PubMed  Google Scholar 

  • Liu K, Li Z, Wu T, Ding S (2011) Role of rho kinase in microvascular damage following cerebral ischemia reperfusion in rats. Int J Mol Sci 12:1222–1231

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Liu FJ, Lim KY, Kaur P, Sepramaniam S, Armugam A, Wong PT, Jeyaseelan K (2013a) MicroRNAs involved in regulating spontaneous recovery in embolic stroke model. PloS One 8:e66393

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Liu X, Li F, Zhao S, Luo Y, Kang J, Zhao H, Yan F, Li S, Ji X (2013b) MicroRNA-124-Mediated Regulation of inhibitory member of apoptosis-stimulating protein of p53 Family in experimental stroke. Stroke 44:1973–1980

    Article  CAS  PubMed  Google Scholar 

  • Manning AL, Dyson NJ (2012) RB: mitotic implications of a tumour suppressor. Nature reviews Cancer 12:220–226

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mishima T, Mizuguchi Y, Kawahigashi Y, Takizawa T (2007) RT-PCR-based analysis of microRNA (miR-1 and -124) expression in mouse CNS. Brain Res 1131:37–43

    Article  CAS  PubMed  Google Scholar 

  • Mott J, Kobayashi S, Bronk S, Gores G (2007) mir-29 regulates Mcl-1 protein expression and apoptosis. Oncogene 26:6133–6140

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ostenfeld M, Bramsen J, Lamy P, Villadsen S, Fristrup N, Sørensen K, Ulhøi B, Borre M, Kjems J, Dyrskjøt L, Orntoft T (2010) miR-145 induces caspase-dependent and -independent cell death in urothelial cancer cell lines with targeting of an expression signature present in Ta bladder tumors. Oncogene 29:1073–1084

    Article  CAS  PubMed  Google Scholar 

  • Ouyang Y, Lu Y, Yue S, Xu L, Xiong X, White R, Sun X, Giffard R (2012) miR-181 regulates GRP78 and influences outcome from cerebral ischemia in vitro and in vivo. Neurobiol Dis 45:555–563

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ozsolak F, Poling L, Wang Z, Liu H, Liu X, Roeder R, Zhang X, Song J, Fisher D (2008) Chromatin structure analyses identify miRNA promoters. Genes Dev 22:3172–3183

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pandi G, Nakka VP, Dharap A, Roopra A, Vemuganti R (2013) MicroRNA miR-29c down-regulation leading to de-repression of its target DNA methyltransferase 3a promotes ischemic brain damage. PloS One 8:e58039

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Schorey JS, Bhatnagar S (2008) Exosome function: from tumor immunology to pathogen biology. Traffic 9:871–881

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Selvamani A, Sathyan P, Miranda R, Sohrabji F (2012) An antagomir to microRNA Let7f promotes neuroprotection in an ischemic stroke model. PLoS One 7:e32662

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Shi G, Liu Y, Liu T, Yan W, Liu X, Wang Y, Shi J, Jia L (2012) Upregulated miR-29b promotes neuronal cell death by inhibiting Bcl2L2 after ischemic brain injury. Exp Brain Res 216:225–230

    Article  CAS  PubMed  Google Scholar 

  • Shi H, Sun BL, Zhang J, Lu S, Zhang P, Wang H, Yu Q, Stetler RA, Vosler PS, Chen J, Gao Y (2013) miR-15b suppression of Bcl-2 contributes to cerebral ischemic injury and is reversed by sevoflurane preconditioning. CNS Neurol Disord Drug Targets 12:381–391

    Article  CAS  PubMed  Google Scholar 

  • Sun Y, Gui H, Li Q, Luo ZM, Zheng MJ, Duan JL, Liu X (2013) MicroRNA-124 protects neurons against apoptosis in cerebral ischemic stroke. CNS Neurosci Ther 19:813–819

    Article  CAS  PubMed  Google Scholar 

  • Veldhuis W, Derksen J, Floris S, Meide PVD, Vries HD, Schepers J, Vos I, Dijkstra C, Kappelle L, Nicolay K, Bär P (2003) Interferon-beta blocks infiltration of inflammatory cells and reduces infarct volume after ischemic stroke in the rat. J Cereb Blood Flow Metab 23:1029–1039

    Article  CAS  PubMed  Google Scholar 

  • Wang F, Li Z (2007) A study on miRNA alternation after H2O2-induced PC12 cell apoptosis using microarray technique. Fa Yi Xue Za Zhi 23:328–331

    CAS  PubMed  Google Scholar 

  • Wang W, Kwon E, Tsai L (2012) MicroRNAs in learning, memory, and neurological diseases. Learn Mem 19:359–368

    Article  CAS  PubMed  Google Scholar 

  • Weiss J, Eisenhardt S, Stark G, Bode C, Moser M, Grundmann S (2012) MicroRNAs in ischemia reperfusion-injury. Am J Cardiovasc Dis 2:237–247

    CAS  PubMed Central  PubMed  Google Scholar 

  • Witwer K, Sisk J, Gama L, Clements J (2010) MicroRNA regulation of IFN-beta protein expression: rapid and sensitive modulation of the innate immune response. J Immunol 184:2369–2376

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ye Z, Huang Y, Wang E, Zuo Z, Guo Q (2012) Sevoflurane-induced delayed neuroprotection involves mitoK(ATP) channel opening and PKC ε activation. Mol Biol Rep 39:5049–5057

    Article  CAS  PubMed  Google Scholar 

  • Yellon D, Hausenloy D (2007) Myocardial reperfusion injury. N Engl J Med 357:1121–1135

    Article  CAS  PubMed  Google Scholar 

  • Yin K, Deng Z, Hamblin M, Xiang Y, Huang H, Zhang J, Jiang X, Wang Y, Chen Y (2010a) Peroxisome proliferator-activated receptor delta regulation of miR-15a in ischemia-induced cerebral vascular endothelial injury. J Neurosci 30:6398–6408

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yin K, Deng Z, Huang H, Hamblin M, Xie C, Zhang J, Chen Y (2010b) miR-497 regulates neuronal death in mouse brain after transient focal cerebral ischemia. Neurobiol Dis 38:17–26

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yuan Y, Wang J, Xu L, Cai R, Chen Z, Luo B (2010) MicroRNA expression changes in the hippocampi of rats subjected to global ischemia. J Clin Neurosci 17:774–778

    Article  CAS  PubMed  Google Scholar 

  • Zhang L, Dong L, Li Y, Hong Z, Wei W (2012) The microRNA miR-181c controls microglia-mediated neuronal apoptosis by suppressing tumor necrosis factor. J Neuroinflammation 9:211

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhu F, Liu JL, Li JP, Xiao F, Zhang ZX, Zhang L (2013) Microrna-124 (mir-124) regulates ku70 expression and is correlated with neuronal death induced by ischemia/reperfusion. J Mol Neurosci 52:148–155

    Article  PubMed  Google Scholar 

  • Ziu M, Fletcher L, Rana S, Jimenez D, Digicaylioglu M (2011) Temporal differences in microRNA expression patterns in astrocytes and neurons after ischemic injury. PLoS One 6:e14724

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Conflict of interest

We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted.

Author information

Authors and Affiliations

  1. Department of Cardiothoracic Surgery, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing, 210008, China

    Yu Di, Yang Lei, Feng Yu, Fan Changfeng, Wang Song & Mo Xuming

Authors
  1. Yu Di
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yang Lei
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Feng Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fan Changfeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wang Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mo Xuming
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mo Xuming.

Additional information

Yu Di and Yang Lei equally contributed to this work

Rights and permissions

Reprints and permissions

About this article

Cite this article

Di, Y., Lei, Y., Yu, F. et al. MicroRNAs Expression and Function in Cerebral Ischemia Reperfusion Injury. J Mol Neurosci 53, 242–250 (2014). https://doi.org/10.1007/s12031-014-0293-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-014-0293-8

Keywords

Search

Navigation