Long Noncoding RNA HOXA-AS3 Integrates NF-κB Signaling To Regulate Endothelium Inflammation

Mol Cell Biol. 2019 Sep 11;39(19):e00139-19. doi: 10.1128/MCB.00139-19. Print 2019 Oct 1.

Abstract

The long noncoding RNA HOXA-AS3 has recently been reported to act as a critical regulator in inflammation-linked lung adenocarcinoma. However, the roles of HOXA-AS3 in endothelium inflammation and related vascular disorders remain poorly defined. In the current study, we identified HOXA-AS3 to be a critical activator to promote NF-κB-mediated endothelium inflammation. HOXA-AS3, a chromatin-associated regulator which colocalizes with NF-κB at specific gene promoters, was found to interact with NF-κB and positively regulate its activity through control of the expression of the NF-κB inhibitor protein IκBα and the acetylation status at the K310 site of p65. More importantly, clinicopathological analysis showed that HOXA-AS3 expression has a significant positive correlation with atherosclerosis. Thus, we conclude that HOXA-AS3 may serve as a crucial biomarker for the clinical diagnosis of atherosclerosis, as well as a promising therapeutic target for the treatment of multiple inflammatory vascular diseases. In addition, this study suggests the functional importance of HOXA-AS3 in the regulation of inflammatory disorders.

Keywords: HOXA-AS3; NF-κB; acetylation; atherosclerosis; endothelium inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Aged
  • Atherosclerosis / genetics*
  • Early Diagnosis
  • Female
  • Genetic Markers / genetics*
  • HEK293 Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Male
  • Middle Aged
  • NF-KappaB Inhibitor alpha / genetics
  • NF-kappa B / metabolism
  • Promoter Regions, Genetic
  • RNA, Long Noncoding / genetics*
  • Signal Transduction*
  • Up-Regulation*

Substances

  • Genetic Markers
  • NF-kappa B
  • RNA, Long Noncoding
  • NF-KappaB Inhibitor alpha