The role of genome-scale leukocyte long noncoding RNA in identifying acute aortic dissection
1Department of Emergency Medicine, Emergency Medical Laboratory, West China Hospital, Sichuan University, 610041 Chengdu, Sichuan, China
2West China Medical School, West China Hospital, Sichuan University, 610041 Chengdu, Sichuan, China
DOI: 10.22514/sv.2022.030 Vol.18,Issue 3,May 2022 pp.101-110
Submitted: 13 November 2021 Accepted: 21 December 2021
Published: 08 May 2022
† These authors contributed equally.
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.
Acute aortic dissection; Long non-coding RNA; Diagnosis; Microarray; Anti-inflammation
Tongyao Li,Yiwu Zhou,Dongze Li,Zhi Zeng,Shu Zhang. The role of genome-scale leukocyte long noncoding RNA in identifying acute aortic dissection. Signa Vitae. 2022. 18(3);101-110.
 Humphrey JD, Schwartz MA, Tellides G, Milewicz DM. Role of mechanotransduction in vascular biology: focus on thoracic aortic aneurysms and dissections. Circulation Research. 2015; 116: 1448–1461.
 Erbel R, Aboyans V, Boileau C, Bossone E, Bartolomeo RD, Eggebrecht H, et al. 2014 ESC guidelines on the diagnosis and treatment of aortic diseases: document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. the task force for the diagnosis and treatment of aortic diseases of the European society of cardiology (ESC). European Heart Journal. 2014; 35: 2873–2926.
 Khan IA, Nair CK. Clinical, diagnostic, and management perspectives of aortic dissection. Chest. 2002; 122: 311–328.
 Wu D, Shen YH, Russell L, Coselli JS, LeMaire SA. Molecular mechanisms of thoracic aortic dissection. Journal of Surgical Research. 2013; 184: 907–924.
 del Porto F, Proietta M, Tritapepe L, Miraldi F, Koverech A, Cardelli P, et al. Inflammation and immune response in acute aortic dissection. Annals of Medicine. 2010; 42: 622–629.
 Chen ZR, Huang B, Lu HS, Zhao ZH, Hui RT, Yang YM, et al. Admission white blood cell count predicts short-term clinical outcomes in patients with uncomplicated stanford type B acute aortic dissection. Journal of geriatric cardiology. 2017; 14: 49–56.
 Fan X, Huang B, Lu H, Zhao Z, Lu Z, Yang Y, et al. Impact of admission white blood cell count on short- and long-term mortality in patients with type a acute aortic dissection: an observational study. Medicine. 2015; 94: e1761.
 Esmon CT. Molecular circuits in thrombosis and inflammation. Throm-bosis and Haemostasis. 2013; 109: 416–420.
 Nagareddy P, Smyth SS. Inflammation and thrombosis in cardiovascular disease. Current Opinion in Hematology. 2013; 20: 457–463.
 Guttman M, Rinn JL. Modular regulatory principles of large non-coding RNAs. Nature. 2012; 482: 339–346.
 An JH, Chen ZY, Ma QL, Wang HJ, Zhang JQ, Shi FW. LncRNA SNHG16 promoted proliferation and inflammatory response of macrophages through miR-17-5p/NF-κB signaling pathway in patients with atherosclerosis. European Review for Medical and Pharmacological Sciences. 2019; 23: 8665–8677.
 Greco S, Gaetano C, Martelli F. Long noncoding competing endogenous RNA networks in age-associated cardiovascular diseases. International Journal of Molecular Sciences. 2019; 20: 3079.
 Shi Q, Yang X. Circulating MicroRNA and long noncoding RNA as biomarkers of cardiovascular diseases. Journal of Cellular Physiology. 2016; 231: 751–755.
 Viereck J, Thum T. Circulating noncoding RNAs as biomarkers of cardiovascular disease and injury. Circulation Research. 2017; 120: 381–399.
 Zhuo X, Wu Y, Yang Y, Gao L, Qiao X, Chen T. LncRNA AK094457 promotes AngII-mediated hypertension and endothelial dysfunction through suppressing of activation of PPARγ. Life Sciences. 2019; 233: 116745.
 Wang XM, Li XM, Song N, Zhai H, Gao XM, Yang YN. Long non-coding RNAs H19, MALAT1 and MIAT as potential novel biomarkers for diag-nosis of acute myocardial infarction. Biomedicine & Pharmacotherapy. 2019; 118: 109208.
 Kanehisa M, Goto S, Kawashima S, Okuno Y, Hattori M. The KEGG resource for deciphering the genome. Nucleic Acids Research. 2004; 32: D277–D2280.
 Barabási A, Oltvai ZN. Network biology: understanding the cell’s functional organization. Nature Reviews Genetics. 2004; 5: 101–113.
 Wang Y, Wu T, Zou L, Xiong L, Zhang T, Kong L, et al. Genome-wide identification and functional analysis of long non-coding RNAs in human endothelial cell line after incubation with PM2.5. Chemosphere. 2019; 216: 396–403.
 Zhai H, Li X, Liu F, Chen BD, Zheng H, Wang X, et al. Expression pattern of genome-scale long noncoding RNA following acute myocardial infarction in Chinese Uyghur patients. Oncotarget. 2017; 8: 31449–31464.
 Zhou XR, Song N, Luo JY, Zhai H, Li XM, Zhao Q, et al. Expression profiles and potential functions of long non-coding RNA in stable angina pectoris patients from Uyghur population of China. Bioscience Reports. 2019; 39: BSR20190364.
 Khananshvili D. The SLC8 gene family of sodium-calcium exchangers NCX- structure, function, and regulation in health and disease. Molecular Aspects of Medicine. 2013; 34: 220–235.
 Tintinger G, Steel HC, Anderson R. Taming the neutrophil: calcium clearance and influx mechanisms as novel targets for pharmacological control. Clinical and Experimental Immunology. 2005; 141: 191–200.
 Vaeth M, Yang J, Yamashita M, Zee I, Eckstein M, Knosp C, et al. ORAI2 modulates store-operated calcium entry and T cell-mediated immunity. Nature Communications. 2017; 8: 14714.
 Liu Z, Jiang L, Li Y, Xie B, Xie J, Wang Z, et al. Cyclosporine a sensitizes lung cancer cells to crizotinib through inhibition of the Ca2+/calcineurin/Erk pathway. EBioMedicine. 2019; 42: 326–339.
 Pan PJ, Tsai JJ, Liu YC. Amentoflavone inhibits metastatic potential through suppression of ERK/NF-κB activation in osteosarcoma U2OS cells. Anticancer Research. 2017; 37: 4911–4918.
 Hiransai P, Ratanachaiyavong S, Itharat A, Graidist P, Ruengrairatanaroj P, Purintrapiban J. Dioscorealide B suppresses LPS-induced nitric oxide production and inflammatory cytokine expression in RAW 264.7 macrophages: the inhibition of NF-kappaB and ERK1/2 activation. Journal of Cellular Biochemistry. 2010; 109: 1057–1063.
 Indra MR, Karyono S, Ratnawati R, Malik SG. Quercetin suppresses inflammation by reducing ERK1/2 phosphorylation and NF kappa B activation in Leptin-induced Human Umbilical Vein Endothelial Cells (HUVECs). BMC Research Notes. 2013; 6: 275.
Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.
Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.
Chemical Abstracts Service Source Index The CAS Source Index (CASSI) Search Tool is an online resource that can quickly identify or confirm journal titles and abbreviations for publications indexed by CAS since 1907, including serial and non-serial scientific and technical publications.
IndexCopernicus The Index Copernicus International (ICI) Journals database’s is an international indexation database of scientific journals. It covered international scientific journals which divided into general information, contents of individual issues, detailed bibliography (references) sections for every publication, as well as full texts of publications in the form of attached files (optional). For now, there are more than 58,000 scientific journals registered at ICI.
Geneva Foundation for Medical Education and Research The Geneva Foundation for Medical Education and Research (GFMER) is a non-profit organization established in 2002 and it works in close collaboration with the World Health Organization (WHO). The overall objectives of the Foundation are to promote and develop health education and research programs.
Scopus: CiteScore 0.5(2021) Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.
Embase Embase (often styled EMBASE for Excerpta Medica dataBASE), produced by Elsevier, is a biomedical and pharmacological database of published literature designed to support information managers and pharmacovigilance in complying with the regulatory requirements of a licensed drug.