GSE118530
Transcriptional profiling of hypoxia-regulated non-coding RNAs in human primary endothelial cells
Hypoxia is human atherosclerotic lesions and has multiple adverse effects on endothelial cell metabolism. Recently, key roles of long non coding RNAs (lncRNAs) in the development of atherosclerosis have begun to emerge. In this study, we investigated the long non-coding RNA profiles of HUVECs subjected to hypoxia using GRO-Seq. We demonstrate that hypoxia regulates the nascent transcription of ~1800 lncRNAs. Interestingly, we provide evidence that promoter associated lncRNAs are more likely to be induced by hypoxia compared to enhancer associated lncRNAs which exhibit equal distribution of up- and downregulated transcripts. We also found that hypoxia leads to significant induction in the activity of superenhancers next to genes and transcription factors implicated in angiogenesis, cell survival and adhesion whereas superenhancers near regulators of peptidyl-tyrosine dephosphorylation, signal transduction and GTPase activity were repressed. Despite majority of lncRNAs exhibiting low detection in RNA-Seq, a subset of lncRNAs were expressed at comparable levels to mRNAs. Among these MALAT1, HYMAI, LOC730101, KIAA1656 and LOC339803 were found differentially expressed in human atherosclerotic and may thus serve as potential biomarkers for lesion hypoxia. Overall design: GRO-Seq and RNA-Seq. Additional datasets for this study can be found under GEO Accession GSE98060 and GSE103945.