缺氧期间长链非编码RNA对血管内皮生长因子A的调控
Long Non-Coding RNA Modulation of VEGF-A during Hypoxia.
作者信息
Nieminen Tiina, Scott Tristan A, Lin Feng-Mao, Chen Zhen, Yla-Herttuala Seppo, Morris Kevin V
机构信息
The Center for Gene Therapy, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
出版信息
Noncoding RNA. 2018 Nov 20;4(4):34. doi: 10.3390/ncrna4040034.
The role and function of long non-coding RNAs (lncRNAs) in modulating gene expression is becoming apparent. Vascular endothelial growth factor A (VEGF-A) is a key regulator of blood vessel formation and maintenance making it a promising therapeutic target for activation in ischemic diseases. In this study, we uncover a functional role for two antisense VEGF-A lncRNAs, and , in transcriptional regulation of during hypoxia. We find here that both lncRNAs are polyadenylated, concordantly upregulated with , localize to the promoter and upstream elements in a hypoxia dependent manner either as a single-stranded RNA or DNA bound RNA, and are associated with enhancer marks H3K27ac and H3K9ac. Collectively, these data suggest that VEGF-A antisense lncRNAs, and , function as promoter enhancer-like elements, possibly by acting as a local scaffolding for proteins and also small RNAs to tether.
长链非编码RNA（lncRNAs）在调节基因表达中的作用和功能正日益显现。血管内皮生长因子A（VEGF-A）是血管形成和维持的关键调节因子，使其成为缺血性疾病中激活治疗的有前景的靶点。在本研究中，我们揭示了两种反义VEGF-A lncRNAs，即 和 ，在缺氧期间对VEGF-A转录调控中的功能作用。我们在此发现，这两种lncRNAs均被多聚腺苷酸化，与VEGF-A协同上调，以单链RNA或DNA结合RNA的形式以缺氧依赖的方式定位于VEGF-A启动子和上游元件，并与增强子标记H3K27ac和H3K9ac相关。总体而言，这些数据表明，VEGF-A反义lncRNAs，即 和 ，可能通过作为蛋白质以及小RNA拴系的局部支架，发挥VEGF-A启动子增强子样元件的作用。
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