Microarray expression profile analysis of long non‐coding RNAs in thoracic aortic aneurysm

Abstract

Thoracic aortic aneurysm (TAA) is a highly lethal vascular disease. Long non-coding RNAs (lncRNAs) are newly discovered as a regulator of protein genes and play critical roles in cardiovascular physio-pathological processes. However, there were a few studies looking at lncRNAs in TAA. In this study, we profiled differential expression of lncRNAs between TAA (TAA group, N = 6) and normal thoracic aorta (control group, n = 6) by third-generation lncRNA microarray. We identified 1352 up-regulated and 1624 down-regulated lncRNAs with differential expression (log fold-change > 2.0, p < 0.01). Through nearby protein-coding gene associated with extracellular matrix (ECM) metabolism and vascular smooth muscle cell (VSMC) apoptosis, 12 up-regulated and 9 down-regulated lncRNAs were selected for further analysis. By calculating phastCons score of base, we identified 8 candidate lncRNAs (4 up-regulated and 4 down-regulated) with high conservation across species. By tissue specificity analysis, we found that 5 lncRNAs (HIF1A-AS1, RP11-465L10.10, LOC100506472, CTD-2184D3.5 and RP-399O19.5) were highly expressed in aortic tissues, suggested that they may be closely associated with TAA. Among them, 2 lncRNAs (RP11-465L10.10 and CTD-2184D3.5) with higher specificity in aorta (p < 0.01) were analyzed by bioinformatics. Further catRAPID analysis revealed a strong RNA-protein interaction between RP11-465L10.10 and myeloid zinc finger gene 1 (MZF1), a transcription factor of MMP9. However, no intense RNA-protein interactions were observed between CTD-2184D3.5 and transcript factors of MAPK6. In conclusions, our study showed differential expression profiles of lncRNAs in TAA and revealed the interaction between certain lncRNAs and coding genes. These data provides insights into new biomarker and therapeutic targets for TAA.

LncRNA LOXL1-AS is up-regulated in thoracic aortic aneurysm and regulated proliferation and apoptosis of aortic smooth muscle cells

“…In another study, lncRNA MALAT1 was also reported to interact with BRG1 to regulate the function of smooth muscle in TAA [14]. Moreover, a recent microarray study revealed a large number of differentially expressed lncRNAs in TAA [15]. Giver participates in inflammation, oxidative stress, and proliferation in vascular smooth muscle cells, which are involved in TAA [12].…”

“…Our preliminary deep sequencing suggested the positive correlation between Giver and LOXL1-AS in TAA. It is known that lncRNAs participate in human diseases mainly by interacting with downstream effector pathways [16,17]. Studies on the interaction between different lncRNAs are rare.…”

Long Noncoding RNAs in Pathological Cardiac Remodeling: A Review of the Update Literature

“…LncRNA-related VSMC dysfunction and ECM degradation were suggested as potential mechanisms according to recent data. Microarray profile analysis revealed that hundreds and thousands of lncRNAs are involved in human thoracic aortic aneurysm (TAA) development, such as Lnc-HLTF-5 [44], HIF1A-AS1, RP11-465L10.10, and CTD-2184D3.5 [45], which might play roles in regulating the expression of MMP-9 in aortic tissue and then facilitate the expansionary remodeling. HIF1alpha-antisense RNA 1 (HIF1A-AS1) was the first reported lncRNA participating in TAA pathogenesis [46].…”

microRNAs in bicuspid aortic valve associated aortopathy: Recent advances and future perspectives

“…More recently, Li et al [64] profiled differential expression of lncRNAs between TAA and normal aortic samples by microarray analysis. Through different filtering steps, the authors selected two TAA-related lncRNAs (RP11-465L10.10 and CTD-2184D3.5) and elaborated their relationship with protein-coding genes, thus providing insights into the research of novel biomarkers and therapeutic targets for TAA [64].…”