Abstract
Stroke is a major cause of premature mortality and disability around the world. Therefore, identification of cellular and molecular processes implicated in the pathogenesis and progression of ischemic stroke has become a priority. Long non-coding RNAs (lncRNAs) are emerging as significant players in the pathophysiology of cerebral ischemia. They are involved in different signalling pathways of cellular processes like cell apoptosis, autophagy, angiogenesis, inflammation, and cell death, impacting the progression of cerebral damage. Exploring the functions of these lncRNAs and their mechanism of action may help in the development of promising treatment strategies. In this review, the current knowledge of lncRNAs in ischemic stroke, focusing on the mechanism by which they cause cellular apoptosis, inflammation, and microglial activation, has been summarized. Very few lncRNAs have been functionally annotated. Therefore, the therapies based on lncRNAs still face many hurdles since the potential targets are likely to increase with the identification of new ones. Majority of experiments involving the identification and function of lncRNAs have been carried out in animal models, and the role of lncRNAs in human stroke presents a challenge. However, mitigating these issues through more rational experimental design might lead to the development of lncRNA-based stroke therapies to treat ischemic stroke.
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References
Krishnamurthi RV, Ikeda T, Feigin VL (2020) Global, Regional and Country-Specific Burden of Ischaemic Stroke, Intracerebral Haemorrhage and Subarachnoid Haemorrhage: a systematic analysis of the Global Burden of Disease Study 2017. Neuroepidemiology 54(2):171–179
Campbell BC, De Silva DA, Macleod MR, Coutts SB, Schwamm LH, Davis SM, Donnan GA (2019) Ischaemic stroke. Nat Rev Dis Prim 5(1):1–22
Bao M-H, Szeto V, Yang BB, Zhu S-Z, Sun H-S, Feng Z-P (2018) Long non-coding RNAs in ischemic stroke. Cell Death Dis 9(3):1–12
Akella A, Bhattarai S, Dharap A (2019) Long noncoding RNAs in the pathophysiology of ischemic stroke. NeuroMolecular Med 21:1–10
Vemuganti R (2013) All’s well that transcribes well: non-coding RNAs and post-stroke brain damage. Neurochem Int 63(5):438–449
He W, Wei D, Cai D, Chen S, Li S, Chen W (2018) Altered long non-coding RNA transcriptomic profiles in ischemic stroke. Hum Gene Ther 29(6):719–732
Kaur H, Sarmah D, Saraf J, Vats K, Kalia K, Borah A, Yavagal DR, Dave KR et al (2018) Noncoding RNAs in ischemic stroke: time to translate. Ann N Y Acad Sci 1421(1):19–36
Wang S-W, Liu Z, Shi Z-S (2018) Non-coding RNA in acute ischemic stroke: mechanisms, biomarkers and therapeutic targets. Cell Transplant 27(12):1763–1777
Ren W, Yang X (2018) Pathophysiology of long non-coding RNAs in ischemic stroke. Front Mol Neurosci 11:96
Dharap A, Nakka VP, Vemuganti R (2012) Effect of focal ischemia on long noncoding RNAs. Stroke 43(10):2800–2802
Chen R, Xu X, Huang L, Zhong W, Cui L (2019a) The regulatory role of long noncoding RNAs in different brain cell types involved in ischemic stroke. Front Mol Neurosci 12:61
Chen Z, Chen X, Guo R, Meng J (2019b) Protective effects of lncRNA H19 silence against hypoxia-induced injury in PC-12 cells by regulating miR-28. Int J Biol Macromol 121:546–555
Yang H, Xi X, Zhao B, Su Z, Wang Z (2018) KLF4 protects brain microvascular endothelial cells from ischemic stroke induced apoptosis by transcriptionally activating MALAT1. Biochem Biophys Res Commun 495(3):2376–2382
Gao Q, Wang Y (2020) Long noncoding RNA MALAT1 regulates apoptosis in ischemic stroke by sponging miR-205-3p and modulating PTEN expression. Am J Transl Res 12(6):2738
Lee E-J, Tournier C (2011) The requirement of uncoordinated 51-like kinase 1 (ULK1) and ULK2 in the regulation of autophagy. Autophagy 7(7):689–695
Guo D, Ma J, Yan L, Li T, Li Z, Han X, Shui S (2017) Down-regulation of Lncrna MALAT1 attenuates neuronal cell death through suppressing Beclin1-dependent autophagy by regulating Mir-30a in cerebral ischemic stroke. Cell Physiol Biochem 43(1):182–194
Henshall DC, Araki T, Schindler CK, Lan J-Q, Tiekoter KL, Taki W, Simon RP (2002) Activation of Bcl-2-associated death protein and counter-response of Akt within cell populations during seizure-induced neuronal death. J Neurosci 22(19):8458–8465
Zhang, J., Rui, Y., Gao, M., Wang, L., & Yan, B. C. (2020a). Expression of long non-coding RNA RGD1566344 in the brain cortex of male mice after focal cerebral ischemia–reperfusion and the neuroprotective effect of a non-coding RNA RGD1566344 inhibitor. Cellular and Molecular Neurobiology.
Zhang L, Yang H, Li W-J, Liu Y-H (2020b) LncRNA MALAT1 promotes OGD-induced apoptosis of brain microvascular endothelial cells by sponging miR-126 to repress PI3K/Akt signaling pathway. Neurochem Res 45(9):2091–2099
Chen J-J, Zhou S-H (2011) Mesenchymal stem cells overexpressing MiR-126 enhance ischemic angiogenesis via the AKT/ERK-related pathway. Cardiol J 18(6):675–681
Chen L, Feng P, Zhu X, He S, Duan J, Zhou D (2016a) Long non-coding RNA Malat1 promotes neurite outgrowth through activation of ERK/MAPK signalling pathway in N2a cells. J Cell Mol Med 20(11):2102–2110
Chen L, Wang J, Wang B, Yang J, Gong Z, Zhao X et al (2016b) MiR-126 inhibits vascular endothelial cell apoptosis through targeting PI3K/Akt signaling. Ann Hematol 95(3):365–374
Wang H-J, Tang X-L, Huang G, Li Y-B, Pan R-H, Zhan J, Wu YK, Liang JF et al (2020a) Long non-coding KCNQ1OT1 promotes oxygen-glucose-deprivation/reoxygenation-induced neurons injury through regulating MIR-153-3p/FOXO3 axis. J Stroke Cerebrovasc Dis 29(10):105126
Wang H, Zheng X, Jin J, Zheng L, Guan T, Huo Y et al (2020b) LncRNA MALAT1 silencing protects against cerebral ischemia-reperfusion injury through miR-145 to regulate AQP4. J Biomed Sci 27(1):1–12
Wang Y, Gu X-X, Huang H-T, Liu C-H, Wei Y-S (2020c) A genetic variant in the promoter of lncRNA MALAT1 is related to susceptibility of ischemic stroke. Lipids Health Dis 19:1–8
Wang Y, Luo Y, Yao Y, Ji Y, Feng L, Du F et al (2020d) Silencing the lncRNA Maclpil in pro-inflammatory macrophages attenuates acute experimental ischemic stroke via LCP1 in mice. J Cereb Blood Flow Metab 40(4):747–759
Cao D-W, Liu M-M, Duan R, Tao Y-F, Zhou J-S, Fang W-R et al (2020) The lncRNA Malat1 functions as a ceRNA to contribute to berberine-mediated inhibition of HMGB1 by sponging miR-181c-5p in poststroke inflammation. Acta Pharmacol Sin 41(1):22–33
Wang J, Cao B, Han D, Sun M, Feng J (2017a) Long non-coding RNA H19 induces cerebral ischemia reperfusion injury via activation of autophagy. Aging Dis 8(1):71–84
Wang J, Zhao H, Fan Z, Li G, Ma Q, Tao Z, Wang R, Feng J et al (2017b) Long noncoding RNA H19 promotes neuroinflammation in ischemic stroke by driving histone Deacetylase 1–dependent M1 microglial polarization. Stroke 48(8):2211–2221
Gao N, Tang H, Gao L, Tu G-L, Luo H, Xia Y (2020) LncRNA H19 aggravates cerebral ischemia/reperfusion injury by functioning as a ceRNA for miR-19a-3p to target PTEN. Neuroscience. 437:117–129
Li, H., Tang, C., & Wang, D. (2020a). FILncRNA H19 promotes inflammatory response induced by cerebral ischemia-reperfusion injury through regulating miR-138-5p/p65. Biochemistry and Cell Biology(ja).
Li H, Yang Y, Hong W, Huang M, Wu M, Zhao X (2020b) Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects. Signal Transduct Targeted Ther 5(1):1–23
Li W, Shen W, Zhang B, Tian K, Li Y, Mu L et al (2020c) Long non-coding RNA LncKdm2b regulates cortical neuronal differentiation by cis-activating Kdm2b. Protein Cell 11(3):161–186
Hu S, Zheng J, Du Z, Wu G (2020) Knock down of lncRNA H19 promotes axon sprouting and functional recovery after cerebral ischemic stroke. Brain Res 1732:146681
Huang J, Yang J, Li J, Chen Z, Guo X, Huang S, Gu L, Su L (2019a) Association of long noncoding RNA H19 polymorphisms with the susceptibility and clinical features of ischemic stroke in southern Chinese Han population. Metab Brain Dis 34(4):1011–1021
Huang Y, Wang L, Mao Y, Nan G (2019b) Long noncoding RNA-H19 contributes to atherosclerosis and induces ischemic stroke via the upregulation of acid phosphatase 5. Front Neurol 10:32
Qi X, Shao M, Sun H, Shen Y, Meng D, Huo W (2017) Long non-coding RNA SNHG14 promotes microglia activation by regulating miR-145-5p/PLA2G4A in cerebral infarction. Neuroscience 348:98–106
Wei R, Zhang L, Hu W, Wu J, Zhang W (2019) Long non-coding RNA AK038897 aggravates cerebral ischemia/reperfusion injury via acting as a ceRNA for miR-26a-5p to target DAPK1. Exp Neurol 314:100–110
Gai H-Y, Wu C, Zhang Y, Wang D (2019) Long non-coding RNA CHRF modulates the progression of cerebral ischemia/reperfusion injury via miR-126/SOX6 signaling pathway. Biochem Biophys Res Commun 514(2):550–557
Fasihi A, Heydari-Zarnagh H, Zahedi M, Goudarzian M, Kafashzadeh M, Meshkani SE, Ramazi S (2020) Study and characterization of long non-coding RUNX1-IT1 among large artery atherosclerosis stroke patients based on the ceRNA hypothesis. J Mol Neurosci 71:1–11
Zhao J, He L, Yin L (2020) lncRNA NEAT1 binds to MiR-339-5p to increase HOXA1 and alleviate ischemic brain damage in neonatal mice. Mol Ther Nucleic Acids 20:117–127
Jing H, Liu L, Jia Y, Yao H, Ma F (2019) Overexpression of the long non-coding RNA Oprm1 alleviates apoptosis from cerebral ischemia-reperfusion injury through the Oprm1/miR-155/GATA3 axis. Artif Cells Nanomed Biotechnol 47(1):2431–2439
Zhong W, Li Y-C, Huang Q-Y, Tang X-Q (2020) lncRNA ANRIL ameliorates oxygen and glucose deprivation (OGD) induced injury in neuron cells via miR-199a-5p/CAV-1 axis. Neurochem Res 45:1–11
Jin R, Yang G, Li G (2010) Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol 87(5):779–789
Hutchinson JN, Ensminger AW, Clemson CM, Lynch CR, Lawrence JB, Chess A (2007) A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains. BMC Genomics 8(1):39
Ji P, Diederichs S, Wang W, Böing S, Metzger R, Schneider PM et al (2003) MALAT-1, a novel noncoding RNA, and thymosin β 4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene 22(39):8031–8041
Ip JY, Nakagawa S (2012) Long non-coding RNAs in nuclear bodies. Develop Growth Differ 54(1):44–54
Nguyen TM, Kabotyanski EB, Reineke LC, Shao J, Xiong F, Lee J-H et al (2020) The SINEB1 element in the long non-coding RNA Malat1 is necessary for TDP-43 proteostasis. Nucleic Acids Res 48(5):2621–2642
Spector DL, Lamond AI (2011) Nuclear speckles. Cold Spring Harb Perspect Biol 3(2):a000646
West JA, Davis CP, Sunwoo H, Simon MD, Sadreyev RI, Wang PI, Tolstorukov MY, Kingston RE (2014) The long noncoding RNAs NEAT1 and MALAT1 bind active chromatin sites. Mol Cell 55(5):791–802
Wang D, Ding L, Wang L, Zhao Y, Sun Z, Karnes RJ, Zhang J, Huang H (2015) LncRNA MALAT1 enhances oncogenic activities of EZH2 in castration-resistant prostate cancer. Oncotarget 6(38):41045–41055
Yang L, Lin C, Liu W, Zhang J, Ohgi KA, Grinstein JD, Dorrestein PC, Rosenfeld MG (2011) ncRNA-and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. Cell 147(4):773–788
Arun G, Aggarwal D, Spector DL (2020) MALAT1 Long non-coding RNA: functional implications. Non-Coding RNA 6(2):22
Li X, Zhou B, Chen L, Gou L-T, Li H, Fu X-D (2017a) GRID-seq reveals the global RNA–chromatin interactome. Nat Biotechnol 35(10):940–950
Li Z, Li J, Tang N (2017b) Long noncoding RNA Malat1 is a potent autophagy inducer protecting brain microvascular endothelial cells against oxygen-glucose deprivation/reoxygenation-induced injury by sponging miR-26b and upregulating ULK2 expression. Neuroscience 354:1–10
Zhang B, Wang D, Ji T-F, Shi L, Yu J-L (2017a) 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 8(10):17347–17359
Zhang J, Yuan L, Zhang X, Hamblin M, Zhu T, Meng F et al (2016) Altered long non-coding RNA transcriptomic profiles in brain microvascular endothelium after cerebral ischemia. Exp Neurol 277:162–170
Zhang X, Tang X, Liu K, Hamblin MH, Yin K-J (2017b) Long noncoding RNA Malat1 regulates cerebrovascular pathologies in ischemic stroke. J Neurosci 37(7):1797–1806
Xin JW, Jiang YG (2017) Long noncoding RNA MALAT1 inhibits apoptosis induced by oxygen-glucose deprivation and reoxygenation in human brain microvascular endothelial cells. Exp Ther Med 13(4):1225–1234
Li H, Gao A, Feng D, Wang Y, Zhang L, Cui Y, Li B, Wang Z et al (2014) Evaluation of the protective potential of brain microvascular endothelial cell autophagy on blood–brain barrier integrity during experimental cerebral ischemia–reperfusion injury. Transl Stroke Res 5(5):618–626
Musiyenko A, Bitko V, Barik S (2008) Ectopic expression of miR-126*, an intronic product of the vascular endothelial EGF-like 7 gene, regulates prostein translation and invasiveness of prostate cancer LNCaP cells. J Mol Med 86(3):313–322
Long G, Wang F, Li H, Yin Z, Sandip C, Lou Y, Wang Y, Chen C et al (2013) Circulating miR-30a, miR-126 and let-7b as biomarker for ischemic stroke in humans. BMC Neurol 13(1):178
Forough R, Weylie B, Collins C, Parker JL, Zhu J, Barhoumi R, Watson DK (2006) Transcription factor Ets-1 regulates fibroblast growth factor-1-mediated angiogenesis in vivo: role of Ets-1 in the regulation of the PI3K/AKT/MMP-1 pathway. J Vasc Res 43(4):327–337
Shultz JC, Goehe RW, Wijesinghe DS, Murudkar C, Hawkins AJ, Shay JW, Minna JD, Chalfant CE (2010) Alternative splicing of caspase 9 is modulated by the phosphoinositide 3-kinase/Akt pathway via phosphorylation of SRp30a. Cancer Res 70(22):9185–9196
Trivedi V, Boire A, Tchernychev B, Kaneider NC, Leger AJ, O’Callaghan K et al (2009) Platelet matrix metalloprotease-1 mediates thrombogenesis by activating PAR1 at a cryptic ligand site. Cell 137(2):332–343
Xin M, Deng X (2005) Nicotine inactivation of the proapoptotic function of Bax through phosphorylation. J Biol Chem 280(11):10781–10789
Disorders NION, Group SRPSS (1995) Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 333(24):1581–1588
Wu L, Xiong X, Wu X, Ye Y, Jian Z, Zhi Z, Gu L (2020) Targeting oxidative stress and inflammation to prevent ischemia-reperfusion injury. Front Mol Neurosci 13:28
Xiao Z, Qiu Y, Lin Y, Medina R, Zhuang S, Rosenblum JS, Cui J, Li Z et al (2019) Blocking lncRNA H19-miR-19a-Id2 axis attenuates hypoxia/ischemia induced neuronal injury. Aging (Albany NY) 11(11):3585–3600
Wang J, Cao B, Zhao H, Gao Y, Luo Y, Chen Y, Feng J (2019) Long noncoding RNA H19 prevents neurogenesis in ischemic stroke through p53/Notch1 pathway. Brain Res Bull 150:111–117
Pedragosa, J., Miró-Mur, F., Otxoa-de-Amezaga, A., Justicia, C., Ruíz-Jaén, F., Ponsaerts, P., . . . Planas, A. M. (2020). CCR2 deficiency in monocytes impairs angiogenesis and functional recovery after ischemic stroke in mice. J Cerebr Blood Flow Metab, 0271678X20909055.
Fang W, Zhai X, Han D, Xiong X, Wang T, Zeng X et al (2018) CCR2-dependent monocytes/macrophages exacerbate acute brain injury but promote functional recovery after ischemic stroke in mice. Theranostics 8(13):3530–3543
Taxin ZH, Neymotin SA, Mohan A, Lipton P, Lytton WW (2014) Modeling molecular pathways of neuronal ischemia. Prog Mol Biol Transl Sci 123:249–275 Elsevier
Liu X, Hou L, Huang W, Gao Y, Lv X, Tang J (2016) 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 10:201
Yan H, Yuan J, Gao L, Rao J, Hu J (2016) Long noncoding RNA MEG3 activation of p53 mediates ischemic neuronal death in stroke. Neuroscience 337:191–199
Wu Z, Wu P, Zuo X, Yu N, Qin Y, Xu Q, He S, Cen B et al (2017) LncRNA-N1LR enhances neuroprotection against ischemic stroke probably by inhibiting p53 phosphorylation. Mol Neurobiol 54(10):7670–7685
Chen F, Zhang L, Wang E, Zhang C, Li X (2018a) LncRNA GAS5 regulates ischemic stroke as a competing endogenous RNA for miR-137 to regulate the Notch1 signaling pathway. Biochem Biophys Res Commun 496(1):184–190
Chen X, Sun Y, Cai R, Wang G, Shu X, Pang W (2018b) Long noncoding RNA: multiple players in gene expression. BMB Rep 51(6):280–289
Xiong Z, Zhang Q, Wang D, Hu L (2018) Overexpression of TUG1 promotes neuronal death after cerebral infarction by regulating microRNA-9. Eur Rev Med Pharmacol Sci 22(21):7393–7400
Chen S, Wang M, Yang H, Mao L, He Q, Jin H, Ye ZM, Luo XY et al (2017) LncRNA TUG1 sponges microRNA-9 to promote neurons apoptosis by up-regulated Bcl2l11 under ischemia. Biochem Biophys Res Commun 485(1):167–173
Alishahi M, Ghaedrahmati F, Kolagar TA, Winlow W, Nikkar N, Farzaneh M, Khoshnam SE (2019) Long non-coding RNAs and cell death following ischemic stroke. Metab Brain Dis 34:1–9
Mehta SL, Kim T, Vemuganti R (2015) Long noncoding RNA FosDT promotes ischemic brain injury by interacting with REST-associated chromatin-modifying proteins. J Neurosci 35(50):16443–16449
Noh K-M, Hwang J-Y, Follenzi A, Athanasiadou R, Miyawaki T, Greally JM, Bennett MVL, Zukin RS (2012) Repressor element-1 silencing transcription factor (REST)-dependent epigenetic remodeling is critical to ischemia-induced neuronal death. Proc Natl Acad Sci 109(16):E962–E971
Xu Q, Deng F, Xing Z, Wu Z, Cen B, Xu S et al (2016) Long non-coding RNA C2dat1 regulates CaMKII δ expression to promote neuronal survival through the NF-κ B signaling pathway following cerebral ischemia. Cell Death Dis 7(3):e2173
Zhang L, Xue Z, Yan J, Wang J, Liu Q, Jiang H (2019) LncRNA Riken-201 and Riken-203 modulates neural development by regulating the Sox6 through sequestering miRNAs. Cell Prolif 52(3):e12573
Kanduri, C. (2011). Kcnq1ot1: a chromatin regulatory RNA. Paper presented at the Seminars in cell & developmental biology.
Knauss JL, Miao N, Kim S-N, Nie Y, Shi Y, Wu T et al (2018) Long noncoding RNA Sox2ot and transcription factor YY1 co-regulate the differentiation of cortical neural progenitors by repressing Sox2. Cell Death Dis 9(8):1–13
Weng R, Lu C, Liu X, Li G, Lan Y, Qiao J et al (2018) Long noncoding RNA-1604 orchestrates neural differentiation through the miR-200c/ZEB axis. Stem Cells 36(3):325–336
Ng S-Y, Bogu GK, Soh BS, Stanton LW (2013) The long noncoding RNA RMST interacts with SOX2 to regulate neurogenesis. Mol Cell 51(3):349–359
Pavlaki I, Alammari F, Sun B, Clark N, Sirey T, Lee S et al (2018) The long non-coding RNA Paupar promotes KAP 1-dependent chromatin changes and regulates olfactory bulb neurogenesis. EMBO J 37(10):e98219
Cheng X, Li H, Zhao H, Li W, Qin J, Jin G (2019) Function and mechanism of long non-coding RNA Gm21284 in the development of hippocampal cholinergic neurons. Cell Biosci 9(1):1–12
Gao Y, Zhang R, Wei G, Dai S, Zhang X, Yang W, Li X, Bai C (2019) Long non-coding RNA maternally expressed 3 increases the expression of neuron-specific genes by targeting miR-128-3p in all-trans retinoic acid-induced neurogenic differentiation from amniotic epithelial cells. Front Cell Dev Biol 7:342
Grammatikakis, I., & Gorospe, M. (2016). Identification of neural stem cell differentiation repressor complex Pnky-PTBP1. Stem Cell Investig, 3.
Michalik KM, You X, Manavski Y, Doddaballapur A, Zörnig M, Braun T et al (2014) Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth. Circ Res 114(9):1389–1397
Liu J, Li Q, Zhang K-S, Hu B, Niu X, Zhou S-M et al (2017) Downregulation of the long non-coding RNA Meg3 promotes angiogenesis after ischemic brain injury by activating notch signaling. Mol Neurobiol 54(10):8179–8190
Zhan R, Xu K, Pan J, Xu Q, Xu S, Shen J (2017) Long noncoding RNA MEG3 mediated angiogenesis after cerebral infarction through regulating p53/NOX4 axis. Biochem Biophys Res Commun 490(3):700–706
Burnside RD, Pasion R, Mikhail FM, Carroll AJ, Robin NH, Youngs EL et al (2011) Microdeletion/microduplication of proximal 15q11. 2 between BP1 and BP2: a susceptibility region for neurological dysfunction including developmental and language delay. Hum Genet 130(4):517–528
Sadikovic B, Fernandes P, Zhang VW, Ward PA, Miloslavskaya I, Rhead W, Rosenbaum R, Gin R et al (2014) Mutation update for UBE 3 A variants in Angelman syndrome. Hum Mutat 35(12):1407–1417
Zhong Y, Yu C, Qin W (2019) LncRNA SNHG14 promotes inflammatory response induced by cerebral ischemia/reperfusion injury through regulating miR-136-5p/ROCK1. Cancer Gene Ther 26(7):234–247
Duan X, Han L, Peng D, Peng C, Xiao L, Bao Q, Peng H (2019) Bioinformatics analysis of a long non-coding RNA and mRNA regulation network in rats with middle cerebral artery occlusion based on RNA sequencing. Mol Med Rep 20(1):417–432
Liu C, Yang J, Zhang C, Liu M, Geng X, Ji X, du H, Zhao H (2018) Analysis of long non-coding RNA expression profiles following focal cerebral ischemia in mice. Neurosci Lett 665:123–129
Wolska M, Jarosz-Popek J, Junger E, Wicik Z, Porshoor T, Sharif L et al (2020) Long non-coding RNAs as promising therapeutic approach in ischemic stroke: a comprehensive review. Mol Neurobiol 58:1–19
Lennox KA, Behlke MA (2016) Cellular localization of long non-coding RNAs affects silencing by RNAi more than by antisense oligonucleotides. Nucleic Acids Res 44(2):863–877
Carlevaro-Fita J, Johnson R (2019) Global positioning system: understanding long noncoding RNAs through subcellular localization. Mol Cell 73(5):869–883
Mercer TR, Dinger ME, Sunkin SM, Mehler MF, Mattick JS (2008) Specific expression of long noncoding RNAs in the mouse brain. Proc Natl Acad Sci 105(2):716–721
Hobuß L, Bär C, Thum T (2019) Long non-coding RNAs: at the heart of cardiac dysfunction? Front Physiol 10:30
Myserlis P, Radmanesh F, Anderson CD (2020) Translational genomics in neurocritical care: a review. Neurotherapeutics 17:1–18
Gomes CP, Spencer H, Ford KL, Michel LY, Baker AH, Emanueli C et al (2017) The function and therapeutic potential of long non-coding RNAs in cardiovascular development and disease. Mol Ther Nucleic Acids 8:494–507
Pedram Fatemi R, Salah-Uddin S, Modarresi F, Khoury N, Wahlestedt C, Faghihi MA (2015) Screening for small-molecule modulators of long noncoding RNA-protein interactions using AlphaScreen. J Biomol Screen 20(9):1132–1141
Awwad DA (2019) Beyond classic editing: innovative CRISPR approaches for functional studies of long non-coding RNA. Biol Method Protocols 4(1):bpz017
Gilbert LA, Horlbeck MA, Adamson B, Villalta JE, Chen Y, Whitehead EH et al (2014) Genome-scale CRISPR-mediated control of gene repression and activation. Cell 159(3):647–661
Hung J, Miscianinov V, Sluimer JC, Newby DE, Baker AH (2018) Targeting non-coding RNA in vascular biology and disease. Front Physiol 9:1655
Khorkova O, Hsiao J, Wahlestedt C (2015) Basic biology and therapeutic implications of lncRNA. Adv Drug Deliv Rev 87:15–24
Zangrando J, Zhang L, Vausort M, Maskali F, Marie P-Y, Wagner DR, Devaux Y (2014) Identification of candidate long non-coding RNAs in response to myocardial infarction. BMC Genomics 15(1):460
Zampetaki A, Albrecht A, Steinhofel K (2018) Long non-coding RNA structure and function: is there a link? Front Physiol 9:1201
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The authors are also grateful to the Central University of Punjab, Bathinda, India, for providing the academic, administrative, and infrastructural support to carry out this work.
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Ms. Kanika Vasudeva is grateful to University Grants Commission (UGC), India, for providing financial assistance in the form of UGC-NET, JRF award.
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Anjana Munshi and Kanika Vasudeva had the idea for the article, Kanika Vasudeva and Anyeasha Dutta performed the literature search, and Anyeasha Dutta and Kanika Vasudeva made the diagrams. Anjana Munshi and Kanika Vasudeva drafted and revised the manuscript. All the authors agreed to all the changes made in the manuscript and submission to Molecular Neurobiology.
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Vasudeva, K., Dutta, A. & Munshi, A. Role of lncRNAs in the Development of Ischemic Stroke and Their Therapeutic Potential. Mol Neurobiol 58, 3712–3728 (2021). https://doi.org/10.1007/s12035-021-02359-0
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DOI: https://doi.org/10.1007/s12035-021-02359-0