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. 2022 Apr;36(4):e24280.
doi: 10.1002/jcla.24280. Epub 2022 Mar 7.

Long non-coding RNA screening and identification of potential biomarkers for type 2 diabetes

Qi Ma  1 , Li Wang  1 , Zhiqiang Wang  2 , Yinxia Su  3 , Qinqin Hou  4 , Qiushuang Xu  5 , Ren Cai  6 , Tingting Wang  7 , Xueli Gong  8 , Qizhong Yi  5
Affiliations

Long non-coding RNA screening and identification of potential biomarkers for type 2 diabetes

Qi Ma et al. J Clin Lab Anal. 2022 Apr.

Abstract

Background: To investigate new lncRNAs as molecular markers of T2D.

Methods: We used microarrays to identify differentially expressed lncRNAs and mRNAs from five patients with T2D and paired controls. Through bioinformatics analysis, qRT-PCR validation, ELISA, and receiver operating characteristic (ROC) curve analysis of 100 patients with T2D and 100 controls to evaluate the correlation between lncRNAs and T2D, and whether lncRNAs could be used in the diagnosis of T2D patients.

Results: We identified 68 and 74 differentially expressed lncRNAs and mRNAs, respectively. The top five upregulated lncRNAs are ENST00000381108.3, ENST00000515544.1, ENST00000539543.1, ENST00000508174.1, and ENST00000564527.1, and the top five downregulated lncRNAs are TCONS_00017539, ENST00000430816.1, ENST00000533203.1, ENST00000609522.1, and ENST00000417079.1. The top five upregulated mRNAs are Q59H50, CYP27A1, DNASE1L3, GRIP2, and lnc-TMEM18-12, and the top five downregulated mRNAs are GSTM4, PODN, GLYATL2, ZNF772, and CLTC. Examination of lncRNA-mRNA interaction pairs indicated that the target gene of lncRNA XR_108954.2 is E2F2. Multiple linear regression analysis showed that XR_108954.2 (r = 0.387, p < 0.01) and E2F2 (r = 0.368, p < 0.01) expression levels were positively correlated with glucose metabolism indicators. Moreover, E2F2 was positively correlated with lipid metabolism indicators (r = 0.333, p < 0.05). The area under the ROC curve was 0.704 (95% CI: 0.578-0.830, p = 0.05) for lncRNA XR_108954.2 and 0.653 (95% CI: 0.516-0.790, p = 0.035) for E2F2.

Conclusions: This transcriptome analysis explored the aberrantly expressed lncRNAs and identified E2F2 and lncRNA XR_108954.2 as potential biomarkers for patients with T2D.

Keywords: biological markers; expression regulation; lncRNA; microarray analysis; type 2 diabetes.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

FIGURE 1
FIGURE 1
Scatter plot analysis of lncRNAs (A) and mRNAs (B) expression
FIGURE 2
FIGURE 2
Gene ontology analysis (A) and Kyoto Encyclopedia of Genes and Genomes pathway analysis (B) of differentially expressed mRNAs
FIGURE 3
FIGURE 3
Co‐expression analysis of lncRNA‐mRNA and lncRNA target gene prediction. Yellow nodes: lncRNAs; green nodes: mRNAs. Red lines: positive correlation; blue lines: negative correlation
FIGURE 4
FIGURE 4
lncRNA XR_108954.2 and E2F2 microarray expression profiling in patients with T2D and controls
FIGURE 5
FIGURE 5
qRT‐PCR and ELISA validation of lncRNA XR_108954.2 and E2F2 expression in patients with T2D patients and controls
FIGURE 6
FIGURE 6
Receiver operating characteristic curve analysis for XR_108954.2 and E2F2
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