Long Noncoding RNA SCIRT Promotes HUVEC Angiogenesis via Stabilizing VEGFA mRNA Induced by Hypoxia.
Long Noncoding RNA SCIRT Promotes HUVEC Angiogenesis via Stabilizing VEGFA mRNA Induced by Hypoxia.
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长非编码 RNA SCIRT 通过稳定缺氧诱导的 VEGFA mRNA 促进 HUVEC 血管生成
DOI：
10.1155/2022/9102978
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发表时间：
2022
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
缺血再灌注损伤（IRI）与长链非编码RNA（lncRNA）的异常表达密切相关，尤其是其在IRI相关血管生成中的调节作用。本研究应用缺氧-复氧（HR）细胞模型来模拟IRI条件，以及RNA测序和RNA下拉实验来揭示lncRNA和干细胞抑制性RNA转录物（SCIRT）在内皮血管生成中的作用。我们发现SCIRT在HR条件下增加，并且与血管生成标记物VEGFA表现出高度的表达相关性。RNA-seq数据分析进一步揭示，在HUVEC中，VEGF相关的血管生成受SCIRT调节。功能获得和丧失实验证明SCIRT通过影响VEGFA mRNA的稳定性对其进行转录后调节。此外，HuR（ELAVL 1），一种RNA结合蛋白（RBP），被鉴定为SCIRT结合伴侣，其结合并稳定VEGFA。此外，SCIRT通过抑制HR条件下HuR的泛素化而促进其表达。这些发现表明，lncRNA SCIRT可以通过在HR条件下调节RBP HuR稳定性来稳定VEGFA mRNA，从而介导内皮血管生成。
Ischemia-reperfusion injury (IRI) is closely associated the abnormal expression of long noncoding RNAs (lncRNAs), especially for their regulatory roles in IRI-related angiogenesis. This study applied a hypoxia-reoxygenation (HR) cell model to simulate the IRI condition, as well as RNA sequencing and RNA pull-down experiments to reveal roles of the lncRNA and Stem Cell Inhibitory RNA Transcript (SCIRT), in endothelial angiogenesis. We found that SCIRT was increased under the HR condition and exhibited a high expression correlation with angiogenesis marker VEGFA. RNA-seq data analysis further revealed that VEGFA-related angiogenesis was regulated by SCIRT in HUVECs. Gain and loss of function experiments proved that SCIRT posttranscriptionally regulated VEGFA via affecting its mRNA stability. Furthermore, HuR (ELAVL1), an RNA binding protein (RBP), was identified as a SCIRT-binding partner, which bound and stabilized VEGFA. Moreover, SCIRT promoted HuR expression posttranslationally by inhibiting its ubiquitination under the HR condition. These findings reveal that lncRNA SCIRT can mediate endothelial angiogenesis by stabilizing the VEGFA mRNA via modulating RBP HuR stability under the HR condition.
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影响因子：
8
作者：
Blanco FF;Jimbo M;Wulfkuhle J;Gallagher I;Deng J;Enyenihi L;Meisner-Kober N;Londin E;Rigoutsos I;Sawicki JA;Risbud MV;Witkiewicz AK;McCue PA;Jiang W;Rui H;Yeo CJ;Petricoin E;Winter JM;Brody JR
通讯作者：
Brody JR
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
4.8
作者：
Fries, Barbara;Heukeshoven, Jochen;Chemnitz, Jan
通讯作者：
Chemnitz, Jan
影响因子：
14.9
作者：
Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
通讯作者：
Flicek P
影响因子：
4.8
作者：
IKEDA, E;ACHEN, MG;RISAU, W
通讯作者：
RISAU, W