4.7 Article

CAD increases the long noncoding RNA PUNISHER in small extracellular vesicles and regulates endothelial cell function via vesicular shuttling

期刊

MOLECULAR THERAPY-NUCLEIC ACIDS
卷 25, 期 -, 页码 388-405

出版社

CELL PRESS
DOI: 10.1016/j.omtn.2021.05.023

关键词

-

资金

  1. German Society of Cardiology (DGK)
  2. German Research Founda-tion (DFG) [WE 4139/8-1, JA 2351/2-1]
  3. Corona Foun-dation
  4. Deutsche Forschungsgemeinschaft (German Research Foundation) [397484323-TRR 259]

向作者/读者索取更多资源

Certain long noncoding RNAs (lncRNAs) are dysregulated in circulating extracellular vesicles of patients with coronary artery disease (CAD). Two lncRNAs, PUNISHER and GAS5, are significantly increased in CAD patients. The intercellular transfer of EV-incorporated PUNISHER promotes a pro-angiogenic phenotype through a VEGFA-dependent mechanism.
Long noncoding RNAs (lncRNAs) have emerged as biomarkers and regulators of cardiovascular disease. However, the expression pattern of circulating extracellular vesicle (EV)-incorporated lncRNAs in patients with coronary artery disease (CAD) is still poorly investigated. A human lncRNA array revealed that certain EV-lncRNAs are significantly dysregulated in CAD patients. Circulating small EVs (sEVs) from patients with (n = 30) or without (n = 30) CAD were used to quantify PUNISHER (also known as AGAP2-antisense RNA 1 [AS1]), GAS5, MALATI, and H19 RNA levels. PUNISHER (p = 0.002) and GAS5 (p = 0.02) were significantly increased in patients with CAD, compared to non-CAD patients. Fluorescent labeling and quantitative real-time PCR of sEVs demonstrated that functional PUNISHER was transported into the recipient cells. Mechanistically, the RNA-binding protein, heterogeneous nuclear ribonucleoprotein K (hnRNPK), interacts with PUNISHER, regulating its loading into sEVs. Knockdown of PUNISHER abrogated the EV-mediated effects on endothelial cell (EC) migration, proliferation, tube formation, and sprouting. Angiogenesis-related gene profiling showed that the expression of vascular endothelial growth factor A (VEGFA) RNA was significantly increased in EV recipient cells. Protein stability and RNA immunoprecipitation indicated that the PUNISHER-hnRNPK axis regulates the stability and binding of VEGFA mRNA to hnRNPK. Loss of PUNISHER in EVs abolished the EV-mediated promotion of VEGFA gene and protein expression. Intercellular transfer of EV-incorporated PUNISHER promotes a pro-angiogenic phenotype via a VEGFA-dependent mechanism.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据