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. 2020 Sep 5:26:e923514.
doi: 10.12659/MSM.923514.

Identification of Hub Genes Associated with Hypertension and Their Interaction with miRNA Based on Weighted Gene Coexpression Network Analysis (WGCNA) Analysis

Zongjin Li  1 , Jacqueline Chyr  2 , Zeyu Jia  3 , Lina Wang  4 , Xi Hu  4 , Xiaoming Wu  4 , Changxin Song  5
Affiliations

Identification of Hub Genes Associated with Hypertension and Their Interaction with miRNA Based on Weighted Gene Coexpression Network Analysis (WGCNA) Analysis

Zongjin Li et al. Med Sci Monit. .

Abstract

BACKGROUND Hypertension is one of the most widespread health conditions in the world, and the molecular mechanism of it is still unclear. In this study, we identified the hub genes (hub miRNA genes) associated with hypertension and explored the relationship between hypertension miRNA-gene by constructing a mRNA co-expression network and a miRNA co-expression network, which can help to reveal the mechanism and predict the prognosis of hypertension progression. MATERIAL AND METHODS Based on gene expression profile data of hypertensive samples from the Gene Expression Omnibus database, WGCNA was used to detect hypertension-related biomarkers and key mRNA and miRNA modules. Then, DAVID was used to perform gene-annotation enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) and miRPath were used for pathway analysis of mRNA and miRNAs genes. RESULTS We identified 3 key modules relating to hypertension, 2 mRNA modules named Msaddlebrown and Mgreenyellow and 1 miRNA module named Msalmon. In addition, 12 hub genes (RPL21, RPS28, LOC442727/PTGAP10, LOC100129599/RPS29P14, TBXAS1, FCER1G, CFP, FURIN, PECAM1, IGSF6, NCF1C, and LOC285296/UNC93B3) and 7 hub miRNAs (hsa-miR-1268a/b, hsa-miR-513c-3p, hsa-miR-4799-5p, hsa-miR-296-3p, hsa-miR-5195-5p, hsa-miR-219-2-3p, and hsa-miR-548d-5p) relating to hypertension were identified. HIF-1 signaling pathway and insulin signaling pathway were closely related to the 3 key modules. We also discovered 4 miRNAs (hsa-miR-548am-3p, hsa-miR-513c-3p, hsa-miR-182-5p, and hsa-miR-548d-5p) and 6 genes (IGF1R, GSK3B, FOXO1, PRKAR2B, HIF1A, and PIK3R1) were the core nodes in the hypertension-related miRNA-gene network, and hsa-miR-548am-3p was at the center of the network. CONCLUSIONS These findings will help improve the understanding of the pathogenesis of hypertension, and the discovered genes can serve as signatures for early diagnosis of hypertension.

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Conflict of interest statement

Conflict of interests

None.

Figures

Figure 1
Figure 1
The workflow of this study.
Figure 2
Figure 2
The cluster dendrogram of mRNA in mRNA expression data, each branch represents a gene, and each color below represents a co-expression module. The first ribbon represents the module detected by dynamic tree cutting, and the second ribbon represents the module after merging the similar module.
Figure 3
Figure 3
The cluster dendrogram of miRNAs in miRNA expression data.
Figure 4
Figure 4
The interaction relationship of co-expressed miRNAs. The different colors in the vertical and horizontal axes stand for different miRNAs modules. The yellow color in the middle area indicated a degree of connection for each miRNA module.
Figure 5
Figure 5
(A) mRNA module-trait relationship. The MESaddlebrown module was most significantly related to hypertension, and the MEGreenyellow module was the second one. (B) miRNA module-trait relationship. The MESalmon module was most significantly related to hypertension.
Figure 6
Figure 6
(A) Module significance of mRNA. Distribution of average mRNA significance and errors in the modules related to hypertension. Salmon module is associated with high blood pressure. (B) Module significance of mRNA.
Figure 7
Figure 7
Volcano map of DEGs for GSE75360 dataset. The red dots on the right corresponds to 2-fold up changes with P-value less than 0.05, and the blue dots on the left means 2-fold down changes with P-value less than 0.05.
Figure 8
Figure 8
The regulatory network of miRNAs and target genes. Among them, the green prisms are mRNA, the purple triangles are miRNA, pink solid lines represent the HIF-1 pathway, and the green dotted lines represent the insulin pathway.
Figure 9
Figure 9
Top 10 nodes in miRNA-gene network.
See this image and copyright information in PMC

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