The role of genome-scale leukocyte long noncoding RNA in identifying acute aortic dissection

Abstract

Acute aortic dissection (AAD) is a disease with intima rupture and explosive inflammatory reaction. In this study, we detected the expression pattern of genome-scale leukocyte long noncoding RNAs (lncRNAs) in patients with AAD and explored the diagnostic efficacy and inflammatory mechanism. The expression levels of lncRNAs and mRNAs in 5 patients with AAD and 5 control cases were detected by microarray technology and were verified in 20 AAD cases and 10 control individuals. A total of 540 up- and 1078 down-regulated lncRNAs were significantly expressed between the two groups. Based on microarray analysis, confirmation through quantitative real-time polymerase chain reaction, and criteria for clinical relevance, three lncRNAs ENST00000430893.1, ENST00000536517.1, and ENST00000593848.1 were identified as potentially important diagnostic lncRNAs of AAD. Receiver operating characteristic curve (ROC curve) analysis showed that the area under curve (AUC) of ENST00000593848.1 was 0.790 (neutrophils, p < 0.05) and 0.725 (monocytes, p < 0.05). The corresponding target gene of ENST00000593848.1 was solute carrier family 8 member A1 (SLC8A1), which encodes a sodium calcium exchanger. Compared with transfection of no-load siRNA group, the Ca2+ levels, interleukin-6 (IL-6) levels, mRNA levels of extracellular regulated kinase (ERK) 1/2, and the activity of P-NF-κB p65 in THP-1 cells were increased after transfection of si-lncRNA (SILNC) (p < 0.05). Together, these results indicate that the three different lncRNAs ENST00000430893.1, ENST00000536517.1, and ENST00000593848.1 may play an anti-inflammatory role in patients with AAD, and ENST00000593848.1 is a promising candidate to further explore as a potential diagnostic and prognostic factor as well as for developing novel therapeutic strategies.