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Regulation of Endothelial Cells by Long Noncoding RNA in Response to Stress

Matthew F Moran, University of Nebraska - Lincoln

Abstract

Regulation of the endothelium is important in maintaining homeostasis in the face of external stressors. Dysregulation of endothelial cells is a major component of several diseases. This regulation can be supplied in the form of long noncoding RNA, which is an understudied and versatile mechanism of regulation in response to stress. To investigate the response of the endothelium to stress, we utilized RNA-seq analysis of HUVECs after induction of a stressor to identify lncRNAs that are differentially expressed in response. Through this, we identified that the lncRNA CRNDE was modulated in response to palmitic acid. CRNDE knockdown reduced endothelial cell proliferation and migration, as well as their angiogenic potential. We also looked at the response of the endothelial cell transcriptome to oxidative stress in the form of H2O2. Using a publicly available dataset, we identified the lncRNA LINC00680 as regulated by oxidative stress. Subsequent RNA-seq of LINC00680 knockdown suggests that LINC00680 has a role in endothelial metabolism and cell cycle progression. We discovered that PTPN7 expression is suppressed by LINC00680 in vitro and in mice and we identified potential protein binding partners of LINC00680 through LC-MS/MS. Together, these results show the multifaceted regulatory landscape of lncRNA and endothelial cells and provide a path to further understand how disease progression affects the endothelium.

Subject Area

Biochemistry|Cellular biology|Molecular biology|Genetics

Recommended Citation

Moran, Matthew F, "Regulation of Endothelial Cells by Long Noncoding RNA in Response to Stress" (2022). ETD collection for University of Nebraska - Lincoln. AAI29167821.
https://digitalcommons.unl.edu/dissertations/AAI29167821

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