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Non-Coding RNA 2018, 4(4), 34; https://doi.org/10.3390/ncrna4040034

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

1
The Center for Gene Therapy, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA
2
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
3
Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA
4
Heart Center and Gene Therapy Unit, Kuopio University Hospital, FI-70211 Kuopio, Finland
*
Author to whom correspondence should be addressed.
Received: 27 September 2018 / Revised: 25 October 2018 / Accepted: 14 November 2018 / Published: 20 November 2018
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Abstract

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, RP1-261G23.7 and EST AV731492, in transcriptional regulation of VEGF-A during hypoxia. We find here that both lncRNAs are polyadenylated, concordantly upregulated with VEGF-A, localize to the VEGF-A 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, RP1-261G23.7 and EST AV731492, function as VEGF-A promoter enhancer-like elements, possibly by acting as a local scaffolding for proteins and also small RNAs to tether. View Full-Text
Keywords: vascular endothelial growth factor A (VEGF-A); long non-coding RNA (lncRNA); transcriptional activation; antisense RNA vascular endothelial growth factor A (VEGF-A); long non-coding RNA (lncRNA); transcriptional activation; antisense RNA
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Nieminen, T.; Scott, T.A.; Lin, F.-M.; Chen, Z.; Yla-Herttuala, S.; Morris, K.V. Long Non-Coding RNA Modulation of VEGF-A during Hypoxia. Non-Coding RNA 2018, 4, 34.

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