Long Noncoding RNA SCIRT Promotes HUVEC Angiogenesis via Stabilizing VEGFA mRNA Induced by Hypoxia

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...

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Published in:Oxidative medicine and cellular longevity 2022, Vol.2022, p.9102978-14
Main Authors: Gao, Lianze, Yang, Jihong, Li, Yi, Liu, Keyu, Sun, Huilin, Tang, Jing, Xia, Zhengyuan, Zhang, Liangqing, Hu, Zhe
Format: Article
Language:English
Subjects:
Angiogenesis
Antibodies
Cell division
Cell Proliferation - genetics
Gene expression
Heart attacks
Humans
Hybridization
Hypoxia
Ischemia
MicroRNAs - metabolism
Neovascularization, Pathologic
Oxidative stress
Proteins
Reagents
RNA, Long Noncoding - genetics
RNA, Long Noncoding - metabolism
RNA, Messenger - genetics
Stem Cells - metabolism
Vascular Endothelial Growth Factor A - genetics
Vascular Endothelial Growth Factor A - metabolism
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Summary: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.
ISSN:1942-0900
1942-0994
DOI:10.1155/2022/9102978