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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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General Review Article

Long Noncoding RNAs as Diagnostic and Therapeutic Targets for Ischemic Stroke

Author(s): Qianwen Wang, Xu Liu and Ruixia Zhu*

Volume 25, Issue 10, 2019

Page: [1115 - 1121] Pages: 7

DOI: 10.2174/1381612825666190328112844

Price: $65

Abstract

LncRNAs (long non-coding RNAs) are endogenous molecules lacking protein-encoding capacity, which have been identified as key regulators of ischemic stroke. Increasing evidence suggests that lncRNAs play critical roles in several aspects of ischemic stroke, including atherosclerosis, dyslipidemia, hypertension, and diabetes mellitus. Hence, lncRNAs may further broaden our understanding of stroke pathogenesis. Altered lncRNA expression has been found in rodent focal cerebral ischemia models and oxygen–glucose deprived mouse brain microvascular endothelial cells as well as stroke patients. LncRNAs are considered to be promising biomarkers for the diagnosis and prognosis of cerebral ischemia. Here, we have reviewed the latest advances in lncRNA-based therapeutic approaches for ischemic disease. Accordingly, we summarize the current understanding of lncRNAs and ischemic stroke, focusing on the regulatory role of lncRNAs in ischemic stroke, as well as their potential as biomarkers and therapeutic targets in cerebral ischemia.

Keywords: LncRNAs, ischemic stroke, etiology, biomarker, diagnosis, therapy.

« Previous Next »
[1]
Benjamin EJ, Virani SS, Callaway CW, et al. Heart Disease and Stroke Statistics-2018 Update: A Report from the American Heart Association. Circulation 2018; 137(12): e67-e492.
[http://dx.doi.org/10.1161/CIR.0000000000000558]
[2]
Donnan GA, Fisher M, Macleod M, Davis SM. Stroke. Lancet 2008; 371(9624): 1612-23.
[http://dx.doi.org/10.1016/S0140-6736(08)60694-7] [PMID: 18468545]
[3]
Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2018; 49(3): e46-e110.
[http://dx.doi.org/10.1161/STR.0000000000000158] [PMID: 29367334]
[4]
Zhang X, Hamblin MH, Yin KJ. The long noncoding RNA Malat1: Its physiological and pathophysiological functions. RNA Biol 2017; 14(12): 1705-14.
[http://dx.doi.org/10.1080/15476286.2017.1358347] [PMID: 28837398]
[5]
Fatica A, Bozzoni I. Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet 2014; 15(1): 7-21.
[http://dx.doi.org/10.1038/nrg3606] [PMID: 24296535]
[6]
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: 98-106.
[http://dx.doi.org/10.1016/j.neuroscience.2017.02.002] [PMID: 28215748]
[7]
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]
[8]
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]
[9]
Lv J, Wang L, Zhang J, et al. Long noncoding RNA H19-derived miR-675 aggravates restenosis by targeting PTEN. Biochem Biophys Res Commun 2018; 497(4): 1154-61.
[http://dx.doi.org/10.1016/j.bbrc.2017.01.011] [PMID: 28063931]
[10]
Han Y, Ma J, Wang J, Wang L. Silencing of H19 inhibits the adipogenesis and inflammation response in ox-LDL-treated Raw264.7 cells by up-regulating miR-130b. Mol Immunol 2018; 93: 107-14.
[http://dx.doi.org/10.1016/j.molimm.2017.11.017] [PMID: 29172088]
[11]
Zhang X, Hamblin MH, Yin KJ. The long noncoding RNA Malat1: Its physiological and pathophysiological functions. RNA Biol 2017; 14(12): 1705-14.
[http://dx.doi.org/10.1080/15476286.2017.1358347] [PMID: 28837398]
[12]
Michalik KM, You X, Manavski Y, et al. Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth. Circ Res 2014; 114(9): 1389-97.
[http://dx.doi.org/10.1161/CIRCRESAHA.114.303265] [PMID: 24602777]
[13]
Yan B, Yao J, Liu JY, et al. lncRNA-MIAT regulates microvascular dysfunction by functioning as a competing endogenous RNA. Circ Res 2015; 116(7): 1143-56.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.305510] [PMID: 25587098]
[14]
Hannou SA, Wouters K, Paumelle R, Staels B. Functional genomics of the CDKN2A/B locus in cardiovascular and metabolic disease: what have we learned from GWASs? Trends Endocrinol Metab 2015; 26(4): 176-84.
[http://dx.doi.org/10.1016/j.tem.2015.01.008] [PMID: 25744911]
[15]
Holdt LM, Hoffmann S, Sass K, et al. Alu elements in ANRIL non-coding RNA at chromosome 9p21 modulate atherogenic cell functions through trans-regulation of gene networks. PLoS Genet 2013; 9(7): e1003588.
[http://dx.doi.org/10.1371/journal.pgen.1003588] [PMID: 23861667]
[16]
Wu G, Cai J, Han Y, et al. LincRNA-p21 regulates neointima formation, vascular smooth muscle cell proliferation, apoptosis, and atherosclerosis by enhancing p53 activity. Circulation 2014; 130(17): 1452-65.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.114.011675] [PMID: 25156994]
[17]
Leung A, Trac C, Jin W, et al. Novel long noncoding RNAs are regulated by angiotensin II in vascular smooth muscle cells. Circ Res 2013; 113(3): 266-78.
[http://dx.doi.org/10.1161/CIRCRESAHA.112.300849] [PMID: 23697773]
[18]
Zou ZQ, Xu J, Li L, Han YS. Down-regulation of SENCR promotes smooth muscle cells proliferation and migration in db/db mice through up-regulation of FoxO1 and TRPC6. Biomed Pharmacother 2015; 74(4): 35-41.
[http://dx.doi.org/10.1016/j.biopha.2015.06.009] [PMID: 26349960]
[19]
Reddy MA, Chen Z, Park JT, et al. Regulation of inflammatory phenotype in macrophages by a diabetes-induced long noncoding RNA. Diabetes 2014; 63(12): 4249-61.
[http://dx.doi.org/10.2337/db14-0298] [PMID: 25008173]
[20]
Hu YW, Yang JY, Ma X, et al. A lincRNA-DYNLRB2-2/GPR119/GLP-1R/ABCA1-dependent signal transduction pathway is essential for the regulation of cholesterol homeostasis. J Lipid Res 2014; 55(4): 681-97.
[http://dx.doi.org/10.1194/jlr.M044669] [PMID: 24493833]
[21]
Ye D, Lammers B, Zhao Y, Meurs I, Van Berkel TJ, Van Eck M. ATP-binding cassette transporters A1 and G1, HDL metabolism, cholesterol efflux, and inflammation: important targets for the treatment of atherosclerosis. Curr Drug Targets 2011; 12(5): 647-60.
[http://dx.doi.org/10.2174/138945011795378522] [PMID: 21039336]
[22]
Hu YW, Ma X, Li XX, et al. Eicosapentaenoic acid reduces ABCA1 serine phosphorylation and impairs ABCA1-dependent cholesterol efflux through cyclic AMP/protein kinase A signaling pathway in THP-1 macrophage-derived foam cells. Atherosclerosis 2009; 204(2): e35-43.
[http://dx.doi.org/10.1016/j.atherosclerosis.2008.11.003] [PMID: 19070858]
[23]
Hu YW, Zhao JY, Li SF, et al. RP5-833A20.1/miR-382-5p/NFIA-dependent signal transduction pathway contributes to the regulation of cholesterol homeostasis and inflammatory reaction. Arterioscler Thromb Vasc Biol 2015; 35(1): 87-101.
[http://dx.doi.org/10.1161/ATVBAHA.114.304296] [PMID: 25265644]
[24]
Halley P, Kadakkuzha BM, Faghihi MA, et al. Regulation of the apolipoprotein gene cluster by a long noncoding RNA. Cell Rep 2014; 6(1): 222-30.
[http://dx.doi.org/10.1016/j.celrep.2013.12.015] [PMID: 24388749]
[25]
Bloch K. The biological synthesis of cholesterol. Science 1965; 150(3692): 19-28.
[http://dx.doi.org/10.1126/science.150.3692.19] [PMID: 5319508]
[26]
Liu G, Zheng X, Xu Y, Lu J, Chen J, Huang X. Long non-coding RNAs expression profile in HepG2 cells reveals the potential role of long non-coding RNAs in the cholesterol metabolism. Chin Med J (Engl) 2015; 128(1): 91-7.
[http://dx.doi.org/10.4103/0366-6999.147824] [PMID: 25563320]
[27]
Miano JM, Long X. The short and long of noncoding sequences in the control of vascular cell phenotypes. Cell Mol Life Sci 2015; 72(18): 3457-88.
[http://dx.doi.org/10.1007/s00018-015-1936-9] [PMID: 26022065]
[28]
Gopalakrishnan K, Kumarasamy S, Mell B, Joe B. Genome-wide identification of long noncoding RNAs in rat models of cardiovascular and renal disease. Hypertension 2015; 65(1): 200-10.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.04498] [PMID: 25385761]
[29]
Bell RD, Long X, Lin M, et al. Identification and initial functional characterization of a human vascular cell-enriched long noncoding RNA. Arterioscler Thromb Vasc Biol 2014; 34(6): 1249-59.
[http://dx.doi.org/10.1161/ATVBAHA.114.303240] [PMID: 24578380]
[30]
Boulberdaa M, Scott E, Ballantyne M, et al. A Role for the Long Noncoding RNA SENCR in Commitment and Function of Endothelial Cells. Mol Ther 2016; 24(5): 978-90.
[http://dx.doi.org/10.1038/mt.2016.41] [PMID: 26898221]
[31]
Das S, Senapati P, Chen Z, et al. Regulation of angiotensin II actions by enhancers and super-enhancers in vascular smooth muscle cells. Nat Comm 2017; 8(1)
[http://dx.doi.org/10.1038/s41467-017-01629-7]
[32]
Yu B, Wang S. Angio-LncRs: LncRNAs that regulate angiogenesis and vascular disease. Theranostics 2018; 8(13): 3654-75.
[http://dx.doi.org/10.7150/thno.26024] [PMID: 30026873]
[33]
Josipovic I, Fork C, Preussner J, et al. PAFAH1B1 and the lncRNA NONHSAT073641 maintain an angiogenic phenotype in human endothelial cells. Acta Physiol (Oxf) 2016; 218(1): 13-27.
[PMID: 27124368]
[34]
Josipovic I, Pflüger B, Fork C, et al. Long noncoding RNA LISPR1 is required for S1P signaling and endothelial cell function. J Mol Cell Cardiol 2018; 116: 57-68.
[http://dx.doi.org/10.1016/j.yjmcc.2018.01.015] [PMID: 29408197]
[35]
Singh KK, Mantella LE, Pan Y, et al. A global profile of glucose-sensitive endothelial-expressed long non-coding RNAs. Can J Physiol Pharmacol 2016; 94(9): 1007-14.
[http://dx.doi.org/10.1139/cjpp-2015-0585] [PMID: 27434139]
[36]
Puthanveetil P, Chen S, Feng B, Gautam A, Chakrabarti S. Long non-coding RNA MALAT1 regulates hyperglycaemia induced inflammatory process in the endothelial cells. J Cell Mol Med 2015; 19(6): 1418-25.
[http://dx.doi.org/10.1111/jcmm.12576] [PMID: 25787249]
[37]
Morán I, Akerman I, van de Bunt M, et al. Human β cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes. Cell Metab 2012; 16(4): 435-48.
[http://dx.doi.org/10.1016/j.cmet.2012.08.010] [PMID: 23040067]
[38]
Wang N, Zhu Y, Xie M, et al. Long Noncoding RNA Meg3 Regulates Mafa Expression in Mouse Beta Cells by Inactivating Rad21, Smc3 or Sin3α. Cell Physiol Biochem 2018; 45(5): 2031-43.
[http://dx.doi.org/10.1159/000487983] [PMID: 29529600]
[39]
Yan B, Yao J, Liu JY, et al. lncRNA-MIAT regulates microvascular dysfunction by functioning as a competing endogenous RNA. Circ Res 2015; 116(7): 1143-56.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.305510] [PMID: 25587098]
[40]
Jin F, Wang N, Zhu Y, et al. Downregulation of Long Noncoding RNA Gas5 Affects Cell Cycle and Insulin Secretion in Mouse Pancreatic β Cells. Cell Physiol Biochem 2017; 43(5): 2062-73.
[http://dx.doi.org/10.1159/000484191] [PMID: 29232661]
[41]
Yin DD, Zhang EB, You LH, et al. Downregulation of lncRNA TUG1 affects apoptosis and insulin secretion in mouse pancreatic β cells. Cell Physiol Biochem 2015; 35(5): 1892-904.
[http://dx.doi.org/10.1159/000373999] [PMID: 25871529]
[42]
Arnes L, Akerman I, Balderes DA, Ferrer J, Sussel L. βlinc1 encodes a long noncoding RNA that regulates islet β-cell formation and function. Genes Dev 2016; 30(5): 502-7.
[http://dx.doi.org/10.1101/gad.273821.115] [PMID: 26944677]
[43]
Dharap A, Nakka VP, Vemuganti R. Effect of focal ischemia on long noncoding RNAs. Stroke 2012; 43(10): 2800-2.
[http://dx.doi.org/10.1161/STROKEAHA.112.669465] [PMID: 22949471]
[44]
Zhang J, Yuan L, Zhang X, et al. Altered long non-coding RNA transcriptomic profiles in brain microvascular endothelium after cerebral ischemia. Exp Neurol 2016; 277: 162-70.
[http://dx.doi.org/10.1016/j.expneurol.2015.12.014] [PMID: 26746985]
[45]
Wu Z, Wu P, Zuo X, et al. LncRNA-N1LR enhances neuroprotection against ischemic stroke probably by inhibiting p53 phosphorylation. Mol Neurobiol 2017; 54(10): 7670-85.
[http://dx.doi.org/10.1007/s12035-016-0246-z] [PMID: 27844279]
[46]
Liu C, Yang J, Zhang C, et al. Analysis of long non-coding RNA expression profiles following focal cerebral ischemia in mice. Neurosci Lett 2018; 665: 123-9.
[http://dx.doi.org/10.1016/j.neulet.2017.11.058] [PMID: 29195908]
[47]
Deng QW, Li S, Wang H, et al. Differential long noncoding RNA expressions in peripheral blood mononuclear cells for detection of acute ischemic stroke. Clin Sci (Lond) 2018; 132(14): 1597-614.
[http://dx.doi.org/10.1042/CS20180411] [PMID: 29997237]
[48]
He W, Wei D, Cai D, Chen S, Li S, Chen W. Altered long non-coding RNA transcriptomic profiles in ischemic stroke. Hum Gene Ther 2018; 29(6): 719-32.
[http://dx.doi.org/10.1089/hum.2017.064] [PMID: 29284304]
[49]
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]
[50]
Gloss B S, Dinger M E. The specificity of long noncoding RNA expression BBA - Gene Regulatory Mechanisms 2016; 1859(1): 16-22.
[http://dx.doi.org/10.1016/j.bbagrm.2015.08.005]
[51]
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]
[52]
Feng L, Guo J, Ai F. Circulating long noncoding RNA ANRIL downregulation correlates with increased risk, higher disease severity and elevated pro-inflammatory cytokines in patients with acute ischemic stroke. Clin Lab Anal 2019; 33(1): e22629.
[53]
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]
[54]
Smith JG, Melander O, Lövkvist H, et al. Common genetic variants on chromosome 9p21 confers risk of ischemic stroke: a large-scale genetic association study. Circ Cardiovasc Genet 2009; 2(2): 159-64.
[http://dx.doi.org/10.1161/CIRCGENETICS.108.835173] [PMID: 20031580]
[55]
Yang J, Gu L, Guo X, et al. LncRNA ANRIL Expression and ANRIL Gene Polymorphisms Contribute to the Risk of Ischemic Stroke in the Chinese Han Population. Cell Mol Neurobiol 2018; 38(6): 1253-69.
[http://dx.doi.org/10.1007/s10571-018-0593-6] [PMID: 29881905]
[56]
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]
[57]
Yan H, Rao J, Yuan J, et al. Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate ischemic neuronal death by targeting miR-21/PDCD4 signaling pathway. Cell Death Dis 2017; 8(12): 3211.
[http://dx.doi.org/10.1038/s41419-017-0047-y] [PMID: 29238035]
[58]
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]
[59]
Zhang X, Tang X, Liu K, Hamblin MH, Yin KJ. Long Noncoding RNA Malat1 Regulates Cerebrovascular Pathologies in Ischemic Stroke. J Neurosci 2017; 37(7): 1797-806.
[http://dx.doi.org/10.1523/JNEUROSCI.3389-16.2017] [PMID: 28093478]
[60]
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: 98-106.
[http://dx.doi.org/10.1016/j.neuroscience.2017.02.002] [PMID: 28215748]

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