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Long Non-coding RNA NORAD Induces Phenotypic Regulation of Vascular Smooth Muscle Cells Through Regulating MicroRNA-136-5p-targeted KDM1A

Overview
Journal Cell Cycle
Specialty Cell Biology
Date 2021 Sep 29
PMID 34583619
Citations 1
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Abstract

Objective: Effect of long non-coding RNAs (lncRNAs) on intracranial aneurysm (IA) development has been identified, while the role of noncoding RNA activated by DNA damage (NORAD) in IA remains unexplored. We aimed to verify the impact of NORAD on IA through sponging microRNA-136-5p (miR-136-5p).

Methods: Ruptured and unruptured IAs were harvested from IA patients, and expression of NORAD, miR-136-5p, and KDM1A was determined. The vascular smooth muscle cells (VSMCs) were cultured and, respectively, transfected with altered NORAD, miR-136-5p, or lysine-specific demethylase 1 (KDM1A) to observe their effect on biological functions, as well as on contraction and synthesis-specific indices of VSMCs. Interactions between NORAD and miR-136-5p, and between miR-136-5p and KDM1A were confirmed.

Results: NORAD and KDM1A were upregulated while miR-136-5p was downregulated in IA, especially in ruptured IA. NORAD overexpression or miR-136-5p inhibition accelerated proliferation and migration, and decelerated phenotypic switching and apoptosis of VSMCs. The effects of overexpressed NORAD on VSMCs were reserved by miR-136-5p upregulation or KDM1A knockdown. NORAD functioned as a competing endogenous RNA of miR-136-5p and miR-136-5p targeted KDM1A.

Conclusion: NORAD suppressed miR-136-5p, thus upregulating KDM1A to participate in IA formation and rupture by inducing phenotypic regulation of VSMCs.

Citing Articles

Prospective Study of lncRNA NORAD for Predicting Cerebrovascular Events in Asymptomatic Patients with Carotid Artery Stenosis.

Fan Y, Ma Y, Wang R, Wang L Clin Appl Thromb Hemost. 2025; 31():10760296241299792.

PMID: 39763215 PMC: 11705339. DOI: 10.1177/10760296241299792.

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