LINC00341 exerts an anti-inflammatory effect on endothelial cells by repressing VCAM1

Tse Shun Huang, Kuei Chun Wang, Sara Quon, Phu Nguyen, Ting Yu Chang, Zhen Chen, Yi Shuan Li, Shankar Subramaniam, John Shyy, Shu Chien

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

The long noncoding RNAs (lncRNAs), which constitute a large portion of the transcriptome, have gained intense research interest because of their roles in regulating physiological and pathophysiological functions in the cell. We identified from RNA-Seq profiling a set of lncRNAs in cultured human umbilical vein endothelial cells (HUVECs) that are differentially regulated by atheroprotective vs. atheroprone shear flows. Among the comprehensively annotated lncRNAs, including both known and novel transcripts, LINC00341 is one of the most abundant lncRNAs in endothelial cells. Moreover, its expression level is enhanced by atheroprotective pulsatile shear flow and atorvastatin. Overexpression of LINC00341 suppresses the expression of vascular cell adhesion molecule 1 (VCAM1) and the adhesion of monocytes induced by atheroprone flow and tumor necrosis factor-alpha. Underlying this anti-inflammatory role, LINC00341 guides enhancer of zest homolog 2, a core histone methyltransferase of polycomb repressive complex 2, to the promoter region of the VCAM1 gene to suppress VCAM1. Network analysis reveals that the key signaling pathways (e.g., Rho and PI3K/AKT) are co-regulated with LINC00341 in endothelial cells in response to pulsatile shear. Together, these findings suggest that LINC00341, as an example of lncRNAs, plays important roles in modulating endothelial function in health and disease.

Original languageEnglish (US)
Pages (from-to)339-345
Number of pages7
JournalPhysiological genomics
Volume49
Issue number7
DOIs
StatePublished - 2017

Keywords

  • EZH2
  • LINC00341
  • Long noncoding RNA
  • Shear stress
  • VCAM1

ASJC Scopus subject areas

  • Physiology
  • Genetics

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