长链非编码核糖核酸及其介导的竞争内源性核糖核酸与卒中发病机制研究进展

doi:10.3969/j.issn.1673-5765.2019.01.012

摘要/Abstract

摘要：

长链非编码核糖核酸（long noncoding RNA，lncRNA）是长度大于200碱基的非编码RNA，为竞争内源性RNA（competing endogenous RNA，ceRNA）的关键组成分子，具有重要的生物学功能。近期研究表明，lncRNA及其介导的ceRNA与卒中的发病、炎症反应及血管生成密切相关，为卒中的诊治提供了新的方向。本文对lncRNA及其介导的ceRNA与卒中关系的研究进展进行综述。

文章导读： 基础和临床研究逐渐发现了越来越多的与卒中相关的长链非编码RNA及其介导的竞争内源性RNA，对其机制的研究有助于更深层次地理解卒中发生发展的机制并进行相应诊疗。

关键词: 卒中; 长链非编码核糖核酸; 竞争内源性核糖核酸

Abstract:

Long noncoding RNA (lncRNA) represents a class of transcripts longer than 200 nucleotides and is a vital molecular component for competing endogenous RNA (ceRNA), which has significant biological function. Recent studies indicated that lncRNA and ceRNA mediated by lncRNA are closely related to the risk of stroke, inflammation and angiogenesis in stroke, which provides a new direction for the diagnosis and treatment of stroke. This article reviewed that the research progress of lncRNA and ceRNA mediated by lncRNA in stroke.

Key words: Stroke; lncRNA; ceRNA

陆小燕，范存秀，杜冰滢，刘振宇，毕晓莹. 长链非编码核糖核酸及其介导的竞争内源性核糖核酸与卒中发病机制研究进展[J]. 中国卒中杂志, 2019, 14(01): 63-68.

LU Xiao-Yan, FAN Cun-Xiu, DU Bing-Ying, LIU Zhen-Yun, BI Xiao-Ying. Research Progress in lncRNA and ceRNA Mediated by lncRNA in Stroke[J]. Chinese Journal of Stroke, 2019, 14(01): 63-68.

参考文献

[1] BENJAMIN E J，VIRANI S S，CALLAWAY C W，

et al. Heart Disease and Stroke Statistics-2018 Update：

A Report From the American Heart Association[J/

OL]. Circulation，2018，137（12）：e67-e492. http：//

doi.org/10.1161/CIR.0000000000000558.

[2] FATICA A，BOZZONI I. Long non-coding

RNAs：new players in cell differentiation and

development[J]. Nat Rev Genet，2014，15（1）：7-21.

[3] TAY Y，RINN J，PANDOLFI PP. The multilayered

complexity of ceRNA crosstalk and competition.

Nature[J]. 2014，505（7483）：344-352.

[4] MEHTA S L，MANHAS N，RAGHUBIR R.

Molecular targets in cerebral ischemia for developing

novel therapeutics[J]. Brain Res Rev，2007，54（1）：

34-66.

[5] HE W Z，WEI D C，CAI D，et al. Altered Long Non-

Coding RNA Transcriptomic Profiles in Ischemic

Stroke[J]. Hum Gene Ther，2018，29（6）：719-732.

[6] ZHANG J，YUAN L，ZHANG X，et al. Altered long

non-coding RNA transcriptomic profiles in brain

microvascular endothelium after cerebral ischemia[J/

OL]. Exp Neurol，2016，277：162-170. https：//doi.

org/10.1016/j.expneurol.2015.12.014.

[7] 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]. J Stroke Cerebrovasc Dis，2018，27（2）：

326-337.

[8] 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[J]. Cell Mol Neurobiol，

2018，38（6）：1253-1269.

[9] WANG J，CAO B，HAN D，et al. Long Non-coding

RNA H19 Induces Cerebral Ischemia Reperfusion

Injury via Activation of Autophagy[J]. Aging Dis，

2017，8（1）：71-84.

[10] ZHANG B，WANG D，JI T F，et al. 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[J]. Oncotarget，

2017，8（10）：17 347-17 359.

[11] LIU J，LI Q，ZHANG K S，et al. Downregulation

of the Long Non-Coding RNA Meg3 Promotes

Angiogenesis After Ischemic Brain Injury by

Activating Notch Signaling[J]. Mol Neurobiol，2017，

54（10）：8179-8190.

[12] ZHAN R，XU K，PAN J，et al. Long noncoding

RNA MEG3 mediated angiogenesis after cerebral

infarction through regulating p53/NOX4 axis[J].

Biochem Biophys Res Commun，2017，490（3）：

700-706.

[13] 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[J]. Stroke，2017，48（8）：

2211-2221.

[14] WEN Y，YU Y，FU X. LncRNA Gm4419

contributes to OGD/R injury of cerebral microglial

cells via IkappaB phosphorylation and NF-kappaB

activation[J]. Biochem Biophys Res Commun，2017，

487（4）：923-929.

[15] 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[J/

OL]. Cell Death Dis，2016，7：e2173. https：//doi.

org/10.1038/cddis.2016.57.

[16] YANG L，LU Z N. Long non-coding RNA HOTAIR

promotes ischemic infarct induced by hypoxia

through up-regulating the expression of NOX2[J].

Biochem Biophys Res Commun，2016，479（2）：

186-191.

[17] ZANG Y，ZHOU X，WANG Q，et al. LncRNA

FIRRE/NF-kB feedback loop contributes to OGD/R injury of cerebral microglial cells[J]. Biochem

Biophys Res Commun，2018，501（1）：131-138.

[18] ZHANG X，TANG X，LIU K，et al. Long

Noncoding RNA Malat1 Regulates Cerebrovascular

Pathologies in Ischemic Stroke[J]. J Neurosci，2017，

37（7）：1797-1806.

[19] MEHTA S L，KIM T，VEMUGANTI R. Long

Noncoding RNA FosDT Promotes Ischemic Brain

Injury by Interacting with REST-Associated

Chromatin-Modifying Proteins[J]. J Neurosci，2015，

35（50）：16 443-16 449.

[20] JIA J，ZHANG M，LI Q，et al. Long noncoding

ribonucleic acid NKILA induces the endoplasmic

reticulum stress/autophagy pathway and inhibits the

nuclear factor-k-gene binding pathway in rats after

intracerebral hemorrhage[J]. J Cell Physiol，2018，

233（11）：8839-8849.

[21] LIANG Z，CHI Y J，LIN G Q，et al. LncRNA

MEG3 participates in neuronal cell injury induced

by subarachnoid hemorrhage via inhibiting the Pi3k/

Akt pathway[J]. Eur Rev Med Pharmacol Sci，2018，

22（9）：2824-2831.

[22] PENG J H，WU Y，TIAN X C，et al. High-

Throughput Sequencing and Co-Expression Network

Analysis of lncRNAs and mRNAs in Early Brain

Injury Following Experimental Subarachnoid

Haemorrhage[J/OL]. Sci Rep，2017，7：46 577. https：

//doi.org/10.1038/srep46577.

[23] WEN J，YANG C Y，LU J，et al. Ptprj-as1 mediates

inflammatory injury after intracerebral hemorrhage

by activating NF-κB pathway[J]. Eur Rev Med

Pharmacol Sci，2018，22（9）：2817-2823.

[24] CHEN F，ZHANG L，WANG E，et al. LncRNA

GAS5 regulates ischemic stroke as a competing

endogenous RNA for miR-137 to regulate the

Notch1 signaling pathway[J]. Biochem Biophys Res

Commun，2018，496（1）：184-190.

[25] CHEN S，WANG M，YANG H，et al. LncRNA

TUG1 sponges microRNA-9 to promote neurons

apoptosis by up-regulated Bcl2l11 under ischemia[J].

Biochem Biophys Res Commun，2017，485（1）：167-

173.

[26] GUO D，MA J，YAN L，et al. Down-Regulation of

Lncrna MALAT1 Attenuates Neuronal Cell Death

Through Suppressing Beclin1-Dependent Autophagy

by Regulating Mir-30a in Cerebral Ischemic

Stroke[J]. Cell Physiol Biochem，2017，43（1）：182-

194.

[27] LI Z，LI J，TANG N. Long noncoding RNA Malat1

is a potent autophagy inducer protecting brain

microvascular endothelial cells against oxygenglucose

deprivation/reoxygenation-induced injury

by sponging miR-26b and upregulating ULK2

expression[J/OL]. Neuroscience，2017，354：1-10.

https：//doi.org/10.1016/j.neuroscience.2017.04.017.

[28] LI L，WANG M，MEI Z，et al. lncRNAs HIF1AAS2

facilitates the up-regulation of HIF-1α by

sponging to miR-153-3p，whereby promoting

angiogenesis in HUVECs in hypoxia[J/OL]. Biomed

Pharmacother，2017，96：165-172. https：//doi.

org/10.1016/j.biopha.2017.09.113.

[29] WANG Z，WANG R，WANG K，et al. Upregulated

long non-coding RNA Snhg1 promotes the

angiogenesis of brain microvascular endothelial

cells after oxygen-glucose deprivation treatment

by targeting miR-199a[J]. Can J Physiol Pharmacol，

2018，96（9）：909-915.

[30] ZHANG L，LUO X，CHEN F，et al. LncRNA

SNHG1 regulates cerebrovascular pathologies

as a competing endogenous RNA through HIF-

1alpha/VEGF signaling in ischemic stroke[J]. J Cell

Biochem，2018，119（7）：5460-5472.

[31] QI X，SHAO M，SUN H，et al. Long non-coding

RNA SNHG14 promotes microglia activation

by regulating miR-145-5p/PLA2G4A in cerebral

infarction[J/OL]. Neuroscience，2017，348：98-106.

https：//doi.org/10.1016/j.neuroscience.2017.02.002.

[32] 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[J]. Cell

Death Dis，2017，8（12）：3211.

[33] DONG B，ZHOU B，SUN Z，et al. LncRNA

FENDRR mediates VEGFA to promote the

apoptosis of brain microvascular endothelial cells

via regulating miR-126 in mice with hypertensive

intracerebral hemorrhage[J/OL]. Microcirculation，

2018，25（8）：e12499. https：//doi.org/10.1111/

micc.12499.