LncRNAs a New Target for Post-Stroke Recovery

Author(s): Jun Yang, Jingjing Zhao, Xu Liu, Ruixia Zhu*

Journal Name: Current Pharmaceutical Design

Volume 26 , Issue 26 , 2020

Become EABM
Become Reviewer
Call for Editor


LncRNAs (long non-coding RNAs) are endogenous molecules, involved in complicated biological processes. Increasing evidence has shown that lncRNAs play a vital role in the post-stroke pathophysiology. Furthermore, several lncRNAs were reported to mediate ischemia cascade processes include apoptosis, bloodbrain barier breakdown, angiogenesis, microglial activation induced neuroinflammation which can cause neuron injury and influence neuron recovery after ischemic stroke. In our study, we first summarize current development about lncRNAs and post-stroke, focus on the regulatory roles of lncRNAs on pathophysiology after stroke. We also reviewed genetic variation in lncRNA associated with functional outcome after ischemic stroke. Additionally, lncRNA-based therapeutics offer promising strategies to decrease brain damage and promote neurological recovery following ischemic stroke. We believe that lncRNAs will become promising for the frontier strategies for IS and can open up a new path for the treatment of IS in the future.

Keywords: LncRNAs, Ischemic stroke, post-stroke, pathophysiology, prognosis, polymorphism.

Liu L, Wang D, Wong KSW, Wang Y. Stroke and stroke care in China: huge burden, significant workload, and a national priority. Stroke 2011; 42(12): 3651-4.
[http://dx.doi.org/10.1161/STROKEAHA.111.635755] [PMID: 22052510]
Aarnio K, Haapaniemi E, Melkas S, Kaste M, Tatlisumak T, Putaala J. Long-term mortality after first-ever and recurrent stroke in young adults. Stroke 2014; 45(9): 2670-6.
[http://dx.doi.org/10.1161/STROKEAHA.114.005648] [PMID: 25061076]
Khoshnam SE, Winlow W, Farzaneh M, Farbood Y, Moghaddam HF. Pathogenic mechanisms following ischemic stroke. Neurol Sci 2017; 38(7): 1167-86.
[http://dx.doi.org/10.1007/s10072-017-2938-1] [PMID: 28417216]
Joy MT, Ben Assayag E, Shabashov-Stone D, et al. CCR5 is a therapeutic target for recovery after stroke and traumatic brain injury. Cell 2019; 176(5): 1143-1157.e13.
[http://dx.doi.org/10.1016/j.cell.2019.01.044] [PMID: 30794775]
Antony M, Scranton V, Srivastava P, Verma R. Micro RNA 181c-5p: A promising target for post-stroke recovery in socially isolated mice. Neurosci Lett 2020; 715 134610
[http://dx.doi.org/10.1016/j.neulet.2019.134610] [PMID: 31722236]
Bao MH, Szeto V, Yang BB, et al. Long non-coding RNAs in ischemic stroke. Cell Death Dis 2018; 9(3): 281.
Zhang X, Hamblin MH, Yin KJ. Noncoding RNAs and Stroke. Neuroscientist 2019; 25(1): 22-6.
[http://dx.doi.org/10.1177/1073858418769556] [PMID: 29637805]
Iyer MK, Niknafs YS, Malik R, et al. The landscape of long noncoding RNAs in the human transcriptome. Nat Genet 2015; 47(3): 199-208.
[http://dx.doi.org/10.1038/ng.3192] [PMID: 25599403]
Dykstra-Aiello C, Jickling GC, Ander BP, et al. Altered expression of long noncoding rnas in blood after ischemic stroke and proximity to putative stroke risk loci. Stroke 2016; 47(12): 2896-903.
[http://dx.doi.org/10.1161/STROKEAHA.116.013869] [PMID: 27834745]
Ramos-Cabrer P, Campos F, Sobrino T, Castillo J. Targeting the ischemic penumbra. Stroke 2011; 42(1)(Suppl.): S7-S11.
[http://dx.doi.org/10.1161/STROKEAHA.110.596684] [PMID: 21164112]
Mehta SL, Kim T, Vemuganti R. Long noncoding RNA FosDT promotes ischemic brain injury by interacting with REST-Associated Chromatin-Modifying Proteins. J Neurosci 2015; 35(50): 16443-9.
[http://dx.doi.org/10.1523/JNEUROSCI.2943-15.2015] [PMID: 26674869]
Xu Q, Deng F, Xing Z, et al. Long non-coding RNA C2dat1 regulates CaMKIIδ expression to promote neuronal survival through the NF-κB signaling pathway following cerebral ischemia. Cell Death Dis 2016; 31: 7. e2173
Chen S, Wang M, Yang H, et al. LncRNA TUG1 sponges microRNA-9 to promote neurons apoptosis by up-regulated Bcl2l11 under ischemia. Biochem Biophys Res Commun 2017; 485(1): 167-73.
[http://dx.doi.org/10.1016/j.bbrc.2017.02.043] [PMID: 28202414]
Zhang T, Wang H, Li Q, Fu J, Huang J, Zhao Y. MALAT1 activates the P53 signaling pathway by regulating mdm2 to promote ischemic stroke. Cell Physiol Biochem 2018; 50(6): 2216-28.
[http://dx.doi.org/10.1159/000495083] [PMID: 30419554]
Wu Z, Wu P, Zuo X, et al. Erratum to: LncRNA-N1LR enhances neuroprotection against ischemic stroke probably by inhibiting p53 phosphorylation. Mol Neurobiol 2017; 54(10): 7686-8.
[http://dx.doi.org/10.1007/s12035-016-0354-9] [PMID: 28054233]
Yan H, Yuan J, Gao L, Rao J, Hu J. Long noncoding RNA MEG3 activation of p53 mediates ischemic neuronal death in stroke. Neuroscience 2016; 337: 191-9.
[http://dx.doi.org/10.1016/j.neuroscience.2016.09.017] [PMID: 27651151]
Zhan R, Xu K, Pan J, Xu Q, Xu S, Shen J. Long noncoding RNA MEG3 mediated angiogenesis after cerebral infarction through regulating p53/NOX4 axis. Biochem Biophys Res Commun 2017; 490(3): 700-6.
[http://dx.doi.org/10.1016/j.bbrc.2017.06.104] [PMID: 28634073]
Liu X, Hou L, Huang W, Gao Y, Lv X, Tang J. The mechanism of long non-coding RNA MEG3 for neurons apoptosis caused by hypoxia: mediated by miR-181b-12/15-LOX signaling pathway. Front Cell Neurosci 2016; 10: 201.
[http://dx.doi.org/10.3389/fncel.2016.00201] [PMID: 27642276]
Zhang A, Zhou N, Huang J, et al. The human long non-coding RNA-RoR is a p53 repressor in response to DNA damage. Cell Res 2013; 23(3): 340-50.
[http://dx.doi.org/10.1038/cr.2012.164] [PMID: 23208419]
Wang Y, Guo Z, Zhao Y, et al. Genetic polymorphisms of lncRNA-p53 regulatory network genes are associated with concurrent chemoradiotherapy toxicities and efficacy in nasopharyngeal carcinoma patients. Sci Rep 2017; 16; 7(1): 8320.
Chen H, Li X. LncRNA ROR is involved in cerebral hypoxia/reoxygenation-induced injury in PC12 cells via regulating miR-135a-5p/ROCK1/2. Am J Transl Res 2019; 11(9): 6145-58.
[PMID: 31632583]
Carniglia L, Ramírez D, Durand D, et al. Neuropeptides and microglial activation in inflammation,pain, and neurodegenerative diseases. Mediat Inflamm 2017; p. 5048616.
Kiernan EA, Smith SM, Mitchell GS, et al. Mechanisms of microglial activation in models of inflammation and hypoxia: implications for chronic intermittent hypoxia. J Physiol 2016; 594(6): 1563. e1577
Qi X, Shao M, Sun H, Shen Y, Meng D, Huo W. Long non-coding RNA SNHG14 promotes microglia activation by regulating miR-145-5p/PLA2G4A in cerebral infarction. Neuroscience 2017; 348(348): 98-106.
[http://dx.doi.org/10.1016/j.neuroscience.2017.02.002] [PMID: 28215748]
Zhang X, Zhu XL, Ji BY, et al. LncRNA-1810034E14Rik reduces microglia activation in experimental ischemic stroke. J Neuroinflammation 2019; 16: 75.
Wen Y, Yu Y, Fu X. LncRNA Gm4419 contributes to OGD/R injury of cerebral microglial cells via IκB phosphorylation and NF-κB activation Biochem Biophys Res Commun 2017 487(4): 923-9.
Wang J, Zhao H, Fan Z, et al. Long noncoding RNA H19 promotes neuroinflammation in ischemic stroke by driving histone deacetylase 1-dependent M1 microglial polarization. Stroke 2017; 48(8): 2211-21.
[http://dx.doi.org/10.1161/STROKEAHA.117.017387] [PMID: 28630232]
Deng Y, Chen D, Wang L, et al. Silencing of long noncoding rna nespas aggravates microglial cell death and neuroinflammation in ischemic stroke. Stroke 2019; 50(7): 1850-8.
[http://dx.doi.org/10.1161/STROKEAHA.118.023376] [PMID: 31167620]
Bai Y, Zhang Y, Han B, et al. Circular RNA DLGAP4 ameliorates ischemic stroke outcomes by targeting mir-143 to regulate endothelial-mesenchymal transition associated with blood-brain barrier integrity J Neurosci 2018; 3;38(1): 3-50.
Navarro-Sobrino M, Rosell A, Hernández-Guillamon M, et al. A large screening of angiogenesis biomarkers and their association with neurological outcome after ischemic stroke. Atherosclerosis 2011; 216(1): 205-11.
[http://dx.doi.org/10.1016/j.atherosclerosis.2011.01.030] [PMID: 21324462]
Hamada Y, Gonda K, Takeda M, et al. In vivo imaging of the molecular distribution of the VEGF receptor during angiogenesis in a mouse model of ischemia. Blood 2011; 118(13): e93-e100.
[http://dx.doi.org/10.1182/blood-2010-12-322842] [PMID: 21821706]
Zhang B, Wang D, Ji TF, Shi L, Yu JL. Overexpression of lncRNA ANRIL up-regulates VEGF expression and promotes angiogenesis of diabetes mellitus combined with cerebral infarction by activating NF-κB signaling pathway in a rat model. Oncotarget 2017; 8(10): 17347-59.
[http://dx.doi.org/10.18632/oncotarget.14468] [PMID: 28060742]
Liu J, Li Q, Zhang KS, et al. Downregulation of the long non-coding RNA Meg3 promotes angiogenesis after ischemic brain injury by activating notch signaling. Mol Neurobiol 2017; 54(10): 8179-90.
[http://dx.doi.org/10.1007/s12035-016-0270-z] [PMID: 27900677]
Wang C, Qu Y, Suo R, Zhu Y. Long non-coding RNA MALAT1 regulates angiogenesis following oxygen-glucose deprivation/reoxygenation. J Cell Mol Med 2019; 23(4): 2970-83.
[http://dx.doi.org/10.1111/jcmm.14204] [PMID: 30784209]
Li L, Wang M, Mei Z, et al. lncRNAs HIF1A-AS2 facilitates the up-regulation of HIF-1α by sponging to miR-153-3p, whereby promoting angiogenesis in HUVECs in hypoxia. Biomed Pharmacother 2017; 96: 165-72.
[http://dx.doi.org/10.1016/j.biopha.2017.09.113] [PMID: 28985553]
Zhao M, Wang J, Xi X, Tan N, Zhang L. SNHG12 Promotes Angiogenesis following ischemic stroke via regulating mir-150/vegf pathway. Neuroscience 2018; 390: 231-40.
[http://dx.doi.org/10.1016/j.neuroscience.2018.08.029] [PMID: 30193860]
Kim YK, Song J. The role of long noncoding RNAs in diabetic Alzheimer ’s disease. J Clin Med 2018; 7(11) E461
[http://dx.doi.org/10.3390/jcm7110461] [PMID: 30469430]
Seaberg RM, van der Kooy D. Adult rodent neurogenic regions: the ventricular subependyma contains neural stem cells, but the dentate gyrus contains restricted progenitors. J Neurosci 2002; 22(5): 1784-93.
[http://dx.doi.org/10.1523/JNEUROSCI.22-05-01784.2002] [PMID: 11880507]
Wang J, Cao B, Zhao H, et al. Long noncoding RNA H19 prevents neurogenesis in ischemic stroke through p53/Notch1 pathway. Brain Res Bull 2019; 150: 111-7.
[http://dx.doi.org/10.1016/j.brainresbull.2019.05.009] [PMID: 31102753]
Pearson-Fuhrhop KM, Burke E, Cramer SC. The influence of genetic factors on brain plasticity and recovery after neural injury. Curr Opin Neurol 2012; 25(6): 682-8.
[http://dx.doi.org/10.1097/WCO.0b013e32835a360a] [PMID: 23044515]
Söderholm M, Pedersen A, Lorentzen E, et al. Genome-wide association meta-analysis of functional outcome after ischemic stroke. Neurology 2019; 92(12): e1271-83.
[http://dx.doi.org/10.1212/WNL.0000000000007138] [PMID: 30796134]
Wu Q, Li T, Zhu D, Lv F, Qin X. Altered expression of long noncoding RNAs in peripheral blood mononuclear cells in patients with impaired leptomeningeal collaterals after acute anterior large vessel occlusions. Ann Transl Med 2019; 7(20): 523.
[http://dx.doi.org/10.21037/atm.2019.10.02] [PMID: 31807505]
Zhu M, Li N, Luo P, et al. Peripheral Blood Leukocyte expression of lncRNA MIAT and its diagnostic and prognostic value in ischemic stroke. J Stroke Cerebrovasc Dis 2018; 27(2): 326-37.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2017.09.009] [PMID: 29030044]
Zhang L, Wang H. Long non-coding RNA in CNS injuries: A new target for therapeutic intervention. Mol Ther Nucleic Acids 2019; 17: 754-66.
[http://dx.doi.org/10.1016/j.omtn.2019.07.013] [PMID: 31437654]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Published on: 11 August, 2020
Page: [3115 - 3121]
Pages: 7
DOI: 10.2174/1381612826666200225141414
Price: $65

Article Metrics

PDF: 29