Exp Clin Endocrinol Diabetes 2017; 125(06): 377-383
DOI: 10.1055/s-0043-100018
Article
© Georg Thieme Verlag KG Stuttgart · New York

The Diagnostic Value of Whole Blood lncRNA ENST00000550337.1 for Pre-Diabetes and Type 2 Diabetes Mellitus

Xuejie Li*
1   Department of Cardiology, People’s Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
,
Zhenzhou Zhao*
1   Department of Cardiology, People’s Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
,
Chuanyu Gao
1   Department of Cardiology, People’s Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
,
Lixin Rao
1   Department of Cardiology, People’s Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
,
Peiyuan Hao
1   Department of Cardiology, People’s Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
,
Dongdong Jian
2   Department of Cardiology, The First Affiliated Hospital of Zhejiang University, Zhejiang University, Hangzhou, China.
,
Wentao Li
1   Department of Cardiology, People’s Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
,
Haiyu Tang
1   Department of Cardiology, People’s Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
,
Muwei Li
1   Department of Cardiology, People’s Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
› Author Affiliations
Further Information

Publication History

Publication Date:
13 April 2017 (online)

Abstract

Background

This study aims to investigate long noncoding RNA (lncRNA) as biomarker for pre-diabetes and T2DM.

Methods

LncRNAs in the peripheral blood of 6 healthy individuals and 6 T2DM patients were collected for microarray analysis. Then 5 candidate biomarkers from the differentially expressed lncRNAs were chosen and verified in a larger independent cohort (control group=20; pre-diabetes group=20; and T2DM group=20). The diagnostic capacity of ENST00000550337.1 was further tested in the third cohort (control group, n=60; pre-diabetes group, n=63; and T2DM group, n=64).

Results

A total of 17 lncRNAs were found to be differentially expressed between the 2 groups. 14 lncRNAs of these were upregulated in T2DM patients and 3 were downregulated. 5 upregulated lncRNAs were selected as potential biomarkers and verified in the second cohort, and the expression levels of 3 lncRNAs increased gradually from the control group to the pre-diabetes group to the T2DM group. The diagnostic value of ENST00000550337.1 was then tested in the third cohort, and its high diagnostic value for pre-diabetes and T2DM was confirmed.

Conclusions

LncRNA ENST00000550337.1 is a potential diagnostic biomarker for pre-diabetes and T2DM.

* These authors contributed equally to this work.


Supplementary Material

 
  • References

  • 1 Mercer TR, Mattick JS. Structure and function of long noncoding RNAs in epigenetic regulation. Nat Struct Mol Biol 2013; 20: 300-307
  • 2 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: 925-938
  • 3 Yoon JH, Abdelmohsen K, Srikantan S. et al. LincRNA-p21 suppresses target mRNA translation. Mol Cell 2012; 47: 648-655
  • 4 Hu W, Yuan B, Flygare J. et al. Long noncoding RNA-mediated anti-apoptotic activity in murine erythroid terminal differentiation. Genes Dev 2011; 25: 2573-2578
  • 5 Guttman M, Donaghey J, Carey BW. et al. lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature 2011; 477: 295-300
  • 6 Zhou X, Yin C, Dang Y. et al. Identification of the long non-coding RNA H19 in plasma as a novel biomarker for diagnosis of gastric cancer. Sci Rep 2015; 5: 11516
  • 7 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: 2695-2698
  • 8 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
  • 9 Moran I, Akerman I, van de Bunt M. et al. Human beta cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes. Cell Metab 2012; 16: 435-448
  • 10 Gao Y, Wu F, Zhou J. et al. The H19/let-7 double-negative feedback loop contributes to glucose metabolism in muscle cells. Nucleic Acids Res 2014; 42: 13799-13811
  • 11 Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998; 15: 539-553
  • 12 Holman RR, Paul SK, Bethel MA. et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008; 359: 1577-1589
  • 13 Gaede P, Lund-Andersen H, Parving HH. et al. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med 2008; 358: 580-591
  • 14 Gatling W, Begley J. Diagnosing diabetes mellitus in clinical practice: is fasting plasma glucose a good initial test?. Practical Diabetes International 2001; 18: 89-93
  • 15 Hung T, Wang Y, Lin MF. et al. Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nat Genet 2011; 43: 621-629
  • 16 Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell 2011; 43: 904-914
  • 17 Thum T, Gross C, Fiedler J. et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature 2008; 456: 980-984
  • 18 Duisters RF, Tijsen AJ, Schroen B. et al. miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling. Circ Res 2009; 104: 170-178 176p following 178
  • 19 van de Bunt M, Gaulton KJ, Parts L. et al. The miRNA profile of human pancreatic islets and beta-cells and relationship to type 2 diabetes pathogenesis. PLoS One 2013; 8: e55272
  • 20 Ferland-McCollough D, Ozanne SE, Siddle K. et al. The involvement of microRNAs in Type 2 diabetes. Biochem Soc Trans 2010; 38: 1565-1570
  • 21 Kornfeld JW, Baitzel C, Konner AC. et al. Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b. Nature 2013; 494: 111-115
  • 22 Yang Z, Chen H, Si H. et al. Serum miR-23a, a potential biomarker for diagnosis of pre-diabetes and type 2 diabetes. Acta Diabetol 2014; 51: 823-831
  • 23 Liu Y, Gao G, Yang C. et al. The role of circulating microRNA-126 (miR-126): a novel biomarker for screening prediabetes and newly diagnosed type 2 diabetes mellitus. Int J Mol Sci 2014; 15: 10567-10577
  • 24 Kumarswamy R, Bauters C, Volkmann I. et al. Circulating long noncoding RNA, LIPCAR, predicts survival in patients with heart failure. Circ Res 2014; 114: 1569-1575
  • 25 Yang Y, Cai Y, Wu G. et al. Plasma long non-coding RNA, CoroMarker, a novel biomarker for diagnosis of coronary artery disease. Clin Sci (Lond) 2015; 129: 675-685