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. 2018 Oct 2;19(1):194.
doi: 10.1186/s12931-018-0894-9.

MiRNA expression profiles in healthy OSAHS and OSAHS with arterial hypertension: potential diagnostic and early warning markers

Xiuping Yang  1 , Xun Niu  1 , Ying Xiao  1 , Kun Lin  1 , Xiong Chen  2
Affiliations

MiRNA expression profiles in healthy OSAHS and OSAHS with arterial hypertension: potential diagnostic and early warning markers

Xiuping Yang et al. Respir Res. .

Abstract

Background: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is prone to being complicated with various cardiovascular, cerebrovascular and metabolic conditions. OSAHS, due to its multifactorial nature, entails individualized and comprehensive treatment. So far, no well-established diagnostic criteria for the disease are available. In recent years, miRNA has been shown to be a sensitive biomarker suggestive of the progression and prognosis of many diseases. In this study, we examined some serum miRNAs in healthy OSAHS (OSAHS patients without complication) and OSAHS with arterial hypertension, with an attempt to understand the potential effects on the disease, improve the diagnosis of OSAHS and find OSAHS-related diagnostic markers.

Methods: Against various diagnostic criteria, participants were divided into three groups: healthy OSAHS, OSAHS with arterial hypertension and healthy controls. Their serum miRNA profiles were assessed by microarray technology, and then differentially expressed miRNAs were verified by quantitative real-time PCR (qRT-PCR). The receiver operating characteristic (ROC) curves of miRNAs were constructed and the areas under the curve (AUC) were calculated. Meanwhile, the miRNAs were subjected to logistic regression analysis. The target genes were bioinformatically assessed, their functions and signaling pathways further determined and eventually an miRNA-gene network was established.

Results: Analysis with the miRNA array exhibited that, compared with the control group, 12 differentially expressed miRNAs were found in healthy OSAHS, and 33 were found in OSAHS with arterial hypertension. The expression of miR-126-3p, let-7d-5p, miR-7641 and miR-1233-5p, miR-320b, miR-145-5p, miR-107, miR-26a-5p were validated by using qRT-PCR. Bioinformatics analysis predicted that the potential target genes of these miRNAs might be involved in metabolism, and the regulation of endothelial cells and nervous system. Moreover, the ROC analysis showed that the using miR-145-5p and let-7d-5p in combination can identify the healthy OSAHS, presence of miR-126-3p, miR-26a-5p and miR-107 was well indicative of OSAHS with arterial hypertension.

Conclusions: A cluster of dysregulation miRNAs have been found to be involved in the development of OSAHS patients. Moreover, these miRNAs might be used to be potential diagnostic and early warning markers.

Keywords: Complications; Diagnostic; Marks; OSAHS; miRNAs.

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Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the Ethics Committee of the Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (2015-S1001), and written informed consent was obtained from all participants.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Hierarchical clustering plot (heatmap) of differentially expressed miRNAs in healthy controls (n = 5), healthy OSAHS (n = 5), OSAHS with arterial hypertension (n = 5). a Healthy OSAHS had dysregulated miRNAs compared to healthy controls (P < 0.05); (b) OSAHS with arterial hypertension had dysregulated miRNAs compared to healthy controls (P < 0.05); (c) 2 overlap miRNAs were up-regulated and the other 2 overlap miRNAs were down-regulated. The right bar represents the signal intensity of miRNA expression from − 2 (green) to 2 (red). Green: down-regulation; red: up-regulation; black: no change
Fig. 2
Fig. 2
qRT-PCR validation of serum miRNA levels in three groups (Group 1: healthy OSAHS, Group 2: OSAHS with arterial hypertension). The relative expression level of (a, b) miR-126-3p, (c, d) let-7d-5p, (e) miR-320b, (f) miR-145-5p, (g) miR-107, (h) miR-26a-5p. The data are expressed as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, NS: no significant changes
Fig. 3
Fig. 3
GO analysis for target genes of validated miRNAs. a the significant GOs of the genes targeted by the validated miRNA in healthy OSAHS. b the significant GOs of the genes targeted by the validated miRNA in OSAHS with arterial hypertension. -LgP is the negative logarithm of the P value. The larger the -LgP value, the smaller the P value, and the more important the roles of GOs
Fig. 4
Fig. 4
Pathway analysis for target genes of validated miRNAs. a the significant pathways of the genes targeted by the validated miRNA in healthy OSAHS. b the significant pathways of the genes targeted by the validated miRNA in OSAHS with arterial hypertension. -LgP is the negative logarithm of the P value. The larger the -LgP value, the smaller the P value, and the more important the roles of pathways
Fig. 5
Fig. 5
miRNA-gene-network. The mauve circles represent genes, the blue squares represent miRNAs, and gray lines represent the relationship between miRNA and genes. The size of the blue square is dependent on the number of genes regulated by an miRNA. a miRNAs-gene-network for the healthy OSAHS; (b) miRNAs-gene-network for OSAHS with arterial hypertension
Fig. 6
Fig. 6
Receiver operating characteristic (ROC) curves analysis of serum miRNAs for three groups (Group 1: healthy OSAHS, Group 2: OSAHS with arterial hypertension). a miR-126-3p, (b) let-7d-5p, (c) miR-320b, (d) miR-145-5p, (e) miR-107, (f) miR-26a-5p. The area under the curve (AUC) was also shown
Fig. 7
Fig. 7
Receiver operating characteristic (ROC) curves for multivariate logistic regression models. a Model 1: multivariate logistic regression model of healthy OSAHS; (b) Model 3: multivariate logistic regression model of OSAHS with arterial hypertension. The area under the curve (AUC) was also shown
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