Long noncoding RNA SNHG12 integrates a DNA-PK-mediated DNA damage response and vascular senescence

Area of Science:

• Vascular Biology
• Molecular Biology
• Genetics

Background:

• Long noncoding RNAs (lncRNAs) are key regulators in the vessel wall.
• The specific role of lncRNAs in atherosclerosis is not well understood.

Purpose of the Study:

• To investigate the function of lncRNAs in atherosclerosis.
• To identify specific lncRNAs involved in lesion progression and regression.

Main Methods:

• RNA sequencing of aortic intima from Ldlr-/- mice during lesion development.
• SNHG12 knockdown and overexpression studies in mouse models.
• LncRNA pulldown assays with LC-MS/MS.
• Analysis of atherosclerotic specimens from pigs and humans.

Main Results:

• Small nucleolar host gene-12 (SNHG12) expression decreases during atherosclerosis progression.
• SNHG12 deficiency accelerates lesion formation by increasing DNA damage and senescence.
• SNHG12 interacts with DNA-dependent protein kinase (DNA-PK), enhancing DNA repair.
• SNHG12 levels are reduced in human and pig atherosclerotic tissues.

Conclusions:

• SNHG12 is a critical regulator of DNA damage response in the vascular endothelium.
• SNHG12 plays a protective role against atherosclerosis.
• SNHG12 may represent a therapeutic target for vascular diseases and aging.