LncRNA MEG8 Attenuates Cerebral Ischemia After Ischemic Stroke Through Targeting miR-130a-5p/VEGFA Signaling

Sui, Shihua; Sun, Lei; Zhang, Wenjing; Li, Jiamei; Han, Jingcui; Zheng, Jiaping; Hua, Xin

doi:10.1007/s10571-020-00904-4

Cited by 45 publications

(21 citation statements)

References 30 publications

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“…MEG8 is found in the 14q32 cluster in humans and 12F1 in mice. Recently, Sui et al showed that downregulation of Meg8, also known as Rian in mice, inhibited cell viability and angiogenesis in mouse brain microvascular ECs, in accordance with our ndings in a HUVEC model [20]. Voellenkle et al showed an upregulation of MEG8 expression in HUVECs exposed to hypoxia [30].…”

Section: Discussionsupporting

confidence: 86%

“…In a study by Zhang et al, MEG8 was found to be downregulated in vascular smooth muscle cells (VSMC) upon ox-LDL stimulation [19]. Furthermore, loss of Meg8 was shown to impair angiogenesis in the mouse, while overexpression of Meg8 was shown to be protective in a rat cerebral ischemia model [20]. We therefore hypothesize that MEG8 could play a protective role in human ECs.…”

Section: Introductionmentioning

confidence: 81%

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MEG8 regulates Tissue Factor Pathway Inhibitor 2 (TFPI2) expression in the endothelium

Kremer

Bink

Stanicek

et al. 2021

Preprint

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A large portion of the genome is transcribed into non-coding RNA, which does not encode protein. Many long non-coding RNAs (lncRNAs) have been shown to be involved in important regulatory processes such as genomic imprinting and chromatin modification. The 14q32 locus contains many non-coding RNAs such as Maternally Expressed Gene 8 (MEG8). We observed an induction of this gene in ischemic heart disease. We investigated the role of MEG8 specifically in endothelial function as well as the underlying mechanism. We hypothesized that MEG8 plays an important role in cardiovascular disease via epigenetic regulation of gene expression. Experiments were performed in human umbilical vein endothelial cells (HUVECs). In vitro silencing of MEG8 resulted in impaired angiogenic sprouting. More specifically, total sprout length was reduced as was proliferation, while migration was unaffected. We performed RNA sequencing to assess changes in gene expression after loss of MEG8. The most profoundly regulated gene, Tissue Factor Pathway Inhibitor 2 (TFPI2), was 5-fold increased following MEG8 silencing. TFPI2 has previously been described as an inhibitor of angiogenesis. Mechanistically, MEG8 silencing resulted in a reduction of the inhibitory histone modification H3K27me3 at the TFPI2 promoter. Interestingly, additional silencing of TFPI2 partially restored angiogenic sprouting capacity but did not affect proliferation of MEG8 silenced cells. In conclusion, silencing of MEG8 impairs endothelial function, suggesting a potential beneficial role in maintaining cell viability. Our study highlights the MEG8/TFPI2 axis as potential therapeutic approach to improve angiogenesis following ischemia.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 81%

MEG8 regulates Tissue Factor Pathway Inhibitor 2 (TFPI2) expression in the endothelium

Kremer

Bink

Stanicek

et al. 2021

Preprint

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“…1f). Existing studies suggest that angiogenesis-related genes contribute to angiogenic remodeling and neurological recovery after IS (Sui et al 2020;Zhang et al 2018). Therefore, we speculate that angiogenesis-related genes in the cyan module may play an important role in the development of IS.…”

Section: Construction Of Co-expression Network and Identi Cation Of Key Modulementioning

confidence: 77%

Construction of a Competitive Endogenous RNA Network Associated with Angiogenesis in Ischemic Stroke Using a Bioinformatics Approach

Wang

Zhang

Xie

et al. 2021

Preprint

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Ischemic stroke (IS) is one of the leading causes of death and disability worldwide, and angiogenesis is an important target for its treatment. However, the mechanism of angiogenesis of endogenous RNA (ceRNA) in IS remains poorly understood. This study aims to explore the role of ceRNA in the angiogenesis of IS, to provide a possible target for the treatment of IS. First, GSE22255 (mRNA), GSE55937 (miRNA) and GSE102541 (lncRNA) were downloaded from the Gene Expression Omnibus (GEO) database. Then, a total of 21 mRNA modules were identified by WGCNA analysis, among which NR4A1, PTGS2, ERG3, and VEGFA in cyan module were identified as key genes for angiogenesis. Subsequently, 1454 differentially expressed lncRNAs (DELs) were screened and a lncRNA-mRNA co-expression network consisting of 40 lncRNAs and 4 mRNAs was constructed by correlation analysis. Then, 16 differentially expressed miRNAs (DEMs) were screened and the online database was used to predict the interaction information between miRNAs, lncRNAs and mRNAs. The angiogenesis-related ceRNA network was finally constructed based on ceRNA theory, in which 1 DEL was predicted as a ceRNA for 2 DEMs to regulate 4 hub genes, specifically, HCG18-has-let-7i-5p-NR4A1/PTGS2/ERG3, HCG18-miR-148a-3p-PTGS2/ERG3/VEGFA interaction axis. The results of gene set enrichment analysis (GSEA) suggest that HCG18 may regulate angiogenesis through NF-kB-TNFA signaling pathway, hypoxia and other pathways. In conclusion, the above genes may be new biomarkers and potential targets for the treatment of IS.

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“…In recent years, long non-coding (Lnc)-RNAs have also been discovered and their biological roles have been demonstrated more clearly. Lnc-SNHG1, H19, MIAT, ZFAS1, MEG8, MALAT1, NEAT1, and TUG1 have been identified for their ability to promote angiogenesis via targeting VEGF expression (Zhao et al, 2017;Hou et al, 2018;Long et al, 2018;Smith et al, 2018;Wang et al, 2018;Zhou et al, 2019;Barth et al, 2020;Li et al, 2020;Sui et al, 2020). Several in vivo delivery studies have confirmed their functional benefit in the prognosis of ischemic injury, especially of the heart and brain.…”

Section: Non-coding Rnas For Angiogenesis In Vivomentioning

confidence: 99%

Rebuilding the Vascular Network: In vivo and in vitro Approaches

Meng

Xing

et al. 2021

Front. Cell Dev. Biol.

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As the material transportation system of the human body, the vascular network carries the transportation of materials and nutrients. Currently, the construction of functional microvascular networks is an urgent requirement for the development of regenerative medicine and in vitro drug screening systems. How to construct organs with functional blood vessels is the focus and challenge of tissue engineering research. Here in this review article, we first introduced the basic characteristics of blood vessels in the body and the mechanism of angiogenesis in vivo, summarized the current methods of constructing tissue blood vessels in vitro and in vivo, and focused on comparing the functions, applications and advantages of constructing different types of vascular chips to generate blood vessels. Finally, the challenges and opportunities faced by the development of this field were discussed.

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LncRNA MEG8 Attenuates Cerebral Ischemia After Ischemic Stroke Through Targeting miR-130a-5p/VEGFA Signaling

Cited by 45 publications

References 30 publications

MEG8 regulates Tissue Factor Pathway Inhibitor 2 (TFPI2) expression in the endothelium

MEG8 regulates Tissue Factor Pathway Inhibitor 2 (TFPI2) expression in the endothelium

Construction of a Competitive Endogenous RNA Network Associated with Angiogenesis in Ischemic Stroke Using a Bioinformatics Approach

Rebuilding the Vascular Network: In vivo and in vitro Approaches

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