hsa-miR-607, lncRNA TUG1 and hsa_circ_0071106 can be combined as biomarkers in type 2 diabetes mellitus

Abstract

Type 2 diabetes mellitus (T2DM) is a multifactorial disorder that leads to alterations in gene regulation. ncRNAs have the characteristics of tissue specificity, disease specificity, timing specificity, high stability and post transcriptional regulation effect. These preconditions are more conducive to promote ncRNA to become a new biomarker for clinical diagnosis. Our study aims to explore the relationship between circRNA, lncRNA, miRNA and T2DM, and to evaluate their diagnostic value for T2DM. A total of 101 pairs of T2DM and controls were conducted in the study. QRT-PCR was used to study the differential expression of circRNAs, miRNAs and lncRNAs. ROC curve was used to estimate their diagnostic value in T2DM. Compared with healthy controls, the expression levels of hsa_circ_0071106, hsa_circ_0000284, hsa_circ_0071271, hsa-miR-29a-5p, hsa-miR-3690, hsa-miR-607, lncRNA MEG3 and lncRNA TUG1were higher in T2DM (all P < 0.05). The AUCs of hsa_circ_0071106, hsa-miR-607 and lncRNA TUG1 for diagnosis of T2DM were 0.563,0.645 and 0.642, respectively. The combined AUC of hsa-miR-607, lncRNA TUG1 and hsa_circ_0071106 was 0.798 ([0.720~0.875], P < 0.001). Moreover, the sensitivity of combined diagnosis was 75.2% and the specificity was 100.0%. The levels of lncRNA TUG1, hsa-miR-607 and hsa_circ_0071106 in peripheral blood have potential clinical diagnostic value for T2DM.

Keywords: ROC; T2DM; circRNA; lncRNA; miRNA.

Figure 1.

hsa_circ_0071106-miRNA interaction network. Red represents hsa_circ_0071106, blue represents predicted miRNA, yellow represents database. (A color version of this figure is available in the online journal.)

Figure 2.

Venn diagrams of bioinformatics predicting lncRNAs interacting with hsa-miR-29a-5p, hsa-miR-607 and hsa-miR-3690. (A color version of this figure is available in the online journal.)

Figure 3.

The ROC curve of ncRNAs in the diagnosis of T2DM. (A) The ROC curve of hsa_circ_0071106 hsa_circ_0071271, hsa_circ_0000284 (B) The ROC curve of hsa-miR-29a-5p, hsa-miR-607, hsa-miR-3690 (C) The ROC curve of lncRNA MEG3 and lncRNA TUG1 (D)The ROC curve of the combination of hsa-miR-607, lncRNA TUG1 and hsa_circ_0071106 in the diagnosis of T2DM. (A color version of this figure is available in the online journal.)

Figure 4.

Correlation between differentially expressed RNAs in peripheral blood and biochemical indexes. **P < 0.05; ***P < 0.001. HDL.C, High density lipoprotein cholesterol; FBG, Fasting blood glucose; LDL.C, Low density lipoprotein cholesterol; TG, Triglycerides; TC, Total cholesterol; SBP, Systolic blood pressure; DBP, Systolic blood pressure; AST, Aspartate transaminase; ALT, Alanine transaminase. (A color version of this figure is available in the online journal.)

Figure 5.

Correlation between differentially expressed ncRNAs in peripheral blood and FBG. (A) Correlation of expression of the hsa-miR-607 in Peripheral Blood and FBG. (B) Correlation of expression of the hsa-miR-3690 in Peripheral Blood and FBG. (C) Correlation of expression of the lncRNA MEG3 in Peripheral Blood and FBG. (D) Correlation of expression of the lncRNA TUG1 in Peripheral Blood and FBG. FBG, Fasting blood glucose. (A color version of this figure is available in the online journal.)