Long Non-Coding RNA Modulation of VEGF-A during Hypoxia

oleh: Tiina Nieminen, Tristan A. Scott, Feng-Mao Lin, Zhen Chen, Seppo Yla-Herttuala, Kevin V. Morris

Format: Article
Diterbitkan: MDPI AG 2018-11-01

Deskripsi

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, <i>RP1-261G23.7</i> and <i>EST AV731492</i>, in transcriptional regulation of <i>VEGF-A</i> during hypoxia. We find here that both lncRNAs are polyadenylated, concordantly upregulated with <i>VEGF-A</i>, localize to the <i>VEGF-A</i> 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, <i>RP1-261G23.7</i> and <i>EST AV731492</i>, function as <i>VEGF-A</i> promoter enhancer-like elements, possibly by acting as a local scaffolding for proteins and also small RNAs to tether.