Vol 25, No 3 (2018)
Original articles — Basic science and experimental cardiology
Published online: 2017-11-14
Identification of a peripheral blood long non-coding RNA (Upperhand) as a potential diagnostic marker of coronary artery disease
Abstract
Background: Long non-coding RNAs (lncRNAs) have been confirmed to be involved in the pathological processes of multiple diseases. However, the characteristic expression of lncRNAs in peripheral blood of coronary artery disease (CAD) patients and whether some of these lncRNAs can be used as diagnostic biomarkers for CAD requires further investigation.
Methods: Six healthy and CAD individuals were selected for microarray analysis, and 5 differentially expressed lncRNAs were selected and confirmed in the second cohort consisting of 30 control individuals and 30 CAD patients with different SYNTAX scores. Upperhand were verified in the third cohort consisting of 115 controls and 137 CAD patients.
Results: Thirty one lncRNAs were differentially expressed between the two groups, among whom, 25 were upregulated in the CAD group and 6 were downregulated. Four of the selected five lncRNAs were significantly upregulated in the CAD group, and Upperhand had the largest area under the curve (AUC). The diagnostic value of Upperhand was tested further, and it remained having a high diagnostic value.
Conclusions: The expression level of Upperhand in peripheral blood of CAD patients is significantly higher than in control individuals, and is correlated with severity of CAD. Upperhand is a potential diagnostic biomarker of CAD, and when combined with TCONS_00029157, diagnostic value slightly increased.
Keywords: coronary artery diseaselong non-coding RNAmicroarray analysisbiomarker
References
- Acharya D, Gulack BC, Loyaga-Rendon RY, et al. Clinical characteristics and outcomes of patients with myocardial infarction and cardiogenic shock undergoing coronary artery bypass surgery: data from the society of thoracic surgeons national database. Ann Thorac Surg. 2016; 101(2): 558–566.
- Waldo SW, Secemsky EA, O'Brien C, et al. Response to letter regarding article, "surgical ineligibility and mortality among patients with unprotected left main or multivessel coronary artery disease undergoing percutaneous coronary intervention". Circulation. 2015; 132(12): e156.
- Mercer TR, Mattick JS. Structure and function of long noncoding RNAs in epigenetic regulation. Nat Struct Mol Biol. 2013; 20(3): 300–307.
- Tripathi V, Ellis JD, Shen Z, et al. The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell. 2010; 39(6): 925–938.
- Yoon JH, Abdelmohsen K, Srikantan S, et al. LincRNA-p21 suppresses target mRNA translation. Mol Cell. 2012; 47(4): 648–655.
- Hu W, Yuan B, Flygare J, et al. Long noncoding RNA-mediated anti-apoptotic activity in murine erythroid terminal differentiation. Genes Dev. 2011; 25(24): 2573–2578.
- Guttman M, Donaghey J, Carey BW, et al. lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature. 2011; 477(7364): 295–300.
- Harries LW. Long non-coding RNAs and human disease. Biochem Soc Trans. 2012; 40(4): 902–906.
- Kitagawa M, Kotake Y, Ohhata T. Long non-coding RNAs involved in cancer development and cell fate determination. Curr Drug Targets. 2012; 13(13): 1616–1621.
- Chubb JE, Bradshaw NJ, Soares DC, et al. The DISC locus in psychiatric illness. Mol Psychiatry. 2008; 13(1): 36–64.
- van de Vondervoort II, Gordebeke PM, Khoshab N, et al. Long non-coding RNAs in neurodevelopmental disorders. Front Mol Neurosci. 2013; 6: 53.
- Liu JY, Yao J, Li XM, et al. Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus. Cell Death Dis. 2014; 5: e1506.
- Lu T, Cui L, Zhou Y, et al. Transcriptome-wide investigation of circular RNAs in rice. RNA. 2015; 21(12): 2076–2087.
- de Kok JB, Verhaegh GW, Roelofs RW, et al. DD3(PCA3), a very sensitive and specific marker to detect prostate tumors. Cancer Res. 2002; 62(9): 2695–2698.
- Xie H, Ma H, Zhou D. Plasma HULC as a promising novel biomarker for the detection of hepatocellular carcinoma. Biomed Res Int. 2013; 2013: 136106.
- Korostowski L, Sedlak N, Engel N. The Kcnq1ot1 long non-coding RNA affects chromatin conformation and expression of Kcnq1, but does not regulate its imprinting in the developing heart. PLoS Genet. 2012; 8(9): e1002956.
- Kumarswamy R, Bauters C, Volkmann I, et al. Circulating long noncoding RNA, LIPCAR, predicts survival in patients with heart failure. Circ Res. 2014; 114(10): 1569–1575.
- Friedrichs F, Zugck C, Rauch GJ, et al. HBEGF, SRA1, and IK: Three cosegregating genes as determinants of cardiomyopathy. Genome Res. 2009; 19(3): 395–403.
- Motterle A, Pu X, Wood H, et al. Functional analyses of coronary artery disease associated variation on chromosome 9p21 in vascular smooth muscle cells. Hum Mol Genet. 2012; 21(18): 4021–4029.
- Holdt LM, Hoffmann S, Sass K, et al. Alu elements in ANRIL non-coding RNA at chromosome 9p21 modulate atherogenic cell functions through trans-regulation of gene networks. PLoS Genet. 2013; 9(7): e1003588.
- Bai Y, Nie S, Jiang G, et al. Regulation of CARD8 expression by ANRIL and association of CARD8 single nucleotide polymorphism rs2043211 (p.C10X) with ischemic stroke. Stroke. 2014; 45(2): 383–388.
- Schiano C, Costa V, Aprile M, et al. Heart failure: Pilot transcriptomic analysis of cardiac tissue by RNA-sequencing. Cardiol J. 2017; 24(5): 539–553.
- Holdt LM, Hoffmann S, Sass K, et al. ANRIL expression is associated with atherosclerosis risk at chromosome 9p21. Arterioscler Thromb Vasc Biol. 2010; 30(3): 620–627.
- Scanlon PJ, Faxon DP, Audet AM, et al. ACC/AHA guidelines for coronary angiography: executive summary and recommendations. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Coronary Angiography) developed in collaboration with the Society for Cardiac Angiography and Interventions. Circulation. 1999; 99(17): 2345–2357.
- Anderson KM, Anderson DM, McAnally JR, et al. Transcription of the non-coding RNA upperhand controls Hand2 expression and heart development. Nature. 2016; 539(7629): 433–436.
- Hitchner E, Zayed M, Varu V, et al. A prospective evaluation of using IVUS during percutaneous superficial femoral artery interventions. Ann Vasc Surg. 2015; 29(1): 28–33.
- Lu Y, Zhang Y, Wang N, et al. MicroRNA-328 contributes to adverse electrical remodeling in atrial fibrillation. Circulation. 2010; 122(23): 2378–2387.
- Li S, Zhu J, Zhang W, et al. Signature microRNA expression profile of essential hypertension and its novel link to human cytomegalovirus infection. Circulation. 2011; 124(2): 175–184.
- Liu W, Ling S, Sun W, et al. Circulating microRNAs correlated with the level of coronary artery calcification in symptomatic patients. Sci Rep. 2015; 5: 16099.
- Sayed D, Hong C, Chen IY, et al. MicroRNAs play an essential role in the development of cardiac hypertrophy. Circ Res. 2007; 100(3): 416–424.
- Meder B, Keller A, Vogel B, et al. MicroRNA signatures in total peripheral blood as novel biomarkers for acute myocardial infarction. Basic Res Cardiol. 2011; 106(1): 13–23.
- Liu Z, Zhou C, Liu Y, et al. The expression levels of plasma micoRNAs in atrial fibrillation patients. PLoS One. 2012; 7(9): e44906.
- Hung T, Wang Y, Lin MF, et al. Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nat Genet. 2011; 43(7): 621–629.
- Tay Y, Rinn J, Pandolfi PP. The multilayered complexity of ceRNA crosstalk and competition. Nature. 2014; 505(7483): 344–352.
- Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011; 43(6): 904–914.
- Yang Y, Cai Y, Wu G, et al. Plasma long non-coding RNA, CoroMarker, a novel biomarker for diagnosis of coronary artery disease. Clinical Science. 2015; 129(8): 675–685.
- Tang DP, Liu LH. The relationship between ECG ST-T changes and the coronary artery disease. Chinese Medical Journal of Metallurgical Industry. 2009.
- Jiang Y, Tian JP, Wang H, et al. Diagnostic value of combined parameters derived from ambulatory electrocardiography for detecting coronary artery disease in non-active chest pain patients. Pak J Med Sci. 2014; 30(6): 1331–1335.
- Zhang J, Wang Y, Guo D. Treadmill exercise test versus coronary computed tomography angiography in diagnosis of coronary atherosclerotic heart disease: Meta-analysis. Chin J Interv Imaging Ther. 2016; 13: 562–566.
