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