Identification of Novel Long Noncoding RNAs and Their Role in Abdominal Aortic Aneurysm.

Abulaihaiti Maitiseyiti,Qingbo Fang,Xiaohu Ge,Sheng Guan,Alimujiang Shawuti,Huguo Wang,Hongbo Ci,Cristiano Caruso

doi:10.1155/2020/3502518

Abstract

Objective Long noncoding RNAs (lncRNAs) have emerged as critical molecular regulators in various diseases. However, the potential regulatory role of lncRNAs in the pathogenesis of abdominal aortic aneurysm (AAA) remains elusive. The aim of this study was to identify crucial lncRNAs associated with human AAA by comparing the lncRNA and mRNA expression profiles of patients with AAA with those of control individuals. Materials and Methods The expression profiles of lncRNAs and mRNAs were analyzed in five dilated aortic samples from AAA patients and three normal aortic samples from control individuals using microarray technology. Functional annotation of the screened lncRNAs based on the differentially expressed genes was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results Microarray results revealed 2046 lncRNAs and 1363 mRNAs. Functional enrichment analysis showed that the mRNAs significantly associated with AAA were enriched in the NOD-like receptor (NLR) and nuclear factor kappa-B (NF-κB) signaling pathways and in cell adhesion molecules (CAMs), which are closely associated with pathophysiological changes in AAA. The lncRNAs identified using microarray analysis were further validated using quantitative real-time polymerase chain reaction (qRT-PCR) analysis with 12 versus 11 aortic samples. Finally, three key lncRNAs (ENST00000566954, ENST00000580897, and T181556) were confirmed using strict validation. A coding-noncoding coexpression (CNC) network and a competing endogenous RNA (ceRNA) network were constructed to determine the interaction among the lncRNAs, microRNAs, and mRNAs based on the confirmed lncRNAs. Conclusions Our microarray profiling analysis and validation of significantly expressed lncRNAs between patients with AAA and control group individuals may provide new diagnostic biomarkers for AAA. The underlying regulatory mechanisms of the confirmed lncRNAs in AAA pathogenesis need to be determined using in vitro and in vivo experiments.

Highlights

Abdominal aortic aneurysm (AAA) is a common, potentially fatal cardiovascular disease characterized by weakening of the local aortic wall, followed by progressive expansion and eventually rupture of the dilated aortic segment [1]
Five dilated abdominal aortic samples from patients with AAA and three normal aortic samples from control subjects obtained during the operation were used in the Long noncoding RNAs (lncRNAs) microarray analysis
AAA patients who are below the currently accepted threshold for surgical intervention have a risk of spontaneous rupture during follow-up owing to the absence of effective drugs to limit the growth of small AAAs [18]

Summary

Introduction

Abdominal aortic aneurysm (AAA) is a common, potentially fatal cardiovascular disease characterized by weakening of the local aortic wall, followed by progressive expansion and eventually rupture of the dilated aortic segment [1]. AAA is generally asymptomatic and occurs in up to 8% of men over the age of 65 years and 1.53% of women over the age of 60 years [2]. The approximately 13000 deaths annually attributed to AAA rupture in the United States are underestimated [3]. There are no effective drugs that can limit the growth of aneurysms and prevent aortic rupture. The detailed mechanisms of AAA progression and the nature of aortic rupture are not fully understood [5]. The hallmark pathological features that lead to AAA formation are complex, including phenotype switching of vascular smooth muscle cells

Methods

Results

Conclusion