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

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.

Key ferroptosis-related genes in abdominal aortic aneurysm formation and rupture as determined by combining bioinformatics techniques

“…TNF-α signaling-induced oxidative stress and apoptosis have been implicated in AAA pathogenesis ( 36 , 37 ). The core role of the Nod-like receptor (NLR) protein family in the innate immune response involves the signal transduction ATP enzyme, which affects atherosclerosis and AAA formation by modulating inflammation that can cause autoimmunity ( 31 , 38 , 39 ). NLRs also play roles in ferroptosis by regulating oxidative stress ( 40 ).…”

Towards a MicroRNAs-Based Biomarker Panel for AIS: A Meta-Analysis

“…Recently, several studies have been focused on characterizing biomarkers 8 to differentiate among the most common stroke subtypes accurately. The non-coding RNAs such as microRNAs (miRNA´s, small single-stranded non-coding RNA molecules from ~22 nucleotides which are endogenously expressed and regulate gene expression though different epigenetic mechanisms) have been proposed as novel biomarkers since they are highly stable and differentially expressed for specific conditions such as cancer, arthritis, osteoporosis, infectious diseases, cardiovascular diseases, neurodegenerative diseases, and AIS [9][10][11] ; miRNA´s are easily isolated from different liquid biopsies such as whole blood, plasma, serum, blood circulating exosomes, peripheral blood cells, or cerebrospinal fluid 12 with low invasiveness for the patients, additionally, it they could be easily measured with conventional labs with the minimum requirements on molecular biology [13][14][15][16][17] .…”