AUTHOR=Qiu Xue , Lin Jinyan , Liang Bixiao , Chen Yanbing , Liu Guoqun , Zheng Jing 

TITLE=Identification of Hub Genes and MicroRNAs Associated With Idiopathic Pulmonary Arterial Hypertension by Integrated Bioinformatics Analyses

JOURNAL=Frontiers in Genetics

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.636934

DOI=10.3389/fgene.2021.636934

ISSN=1664-8021

ABSTRACT=Objective: Identification of hub genes associated with idiopathic pulmonary arterial hypertension (IPAH).
Materials and Methods: GSE15197 gene expression data was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by screening IPAH patients and controls. The 5000 genes with the greatest variances were analysed using weighted gene co-expression network analysis (WGCNA). Modules with the strongest correlation with IPAH were chosen, followed by functional enrichment analysis. Protein-protein interaction (PPI) networks were constructed to identify hub gene candidates using calculated degrees. Real hub genes were found from the overlap of DEGs and candidate hub genes. microRNAs (miRNAs) targeting real hub genes were found by screening miRNet 2.0. The most important IPAH miRNAs were identified.
Results: 4395 DEGs were identified. WGCNA analysis indicated that green and brown modules associated most strongly with IPAH. Functional enrichment analysis showed that green and brown module genes were mainly involved in protein digestion and absorption and proteoglycans in cancer respectively. Top ten candidate hub genes in green and brown modules were identified respectively. After overlapping with DEGs, 11 real hub genes were identified: EP300, MMP2, CDH2, CDK2, GNG10, ALB, SMC2, DHX15, CUL3, BTBD1 and LTN1. These genes were expressed with significant differences in IPAH versus controls, indicating a high diagnostic ability. The miRNA-gene network showed that hsa-mir-1-3p could associate with IPAH. 
Conclusions: EP300, MMP2, CDH2, CDK2, GNG10, ALB, SMC2, DHX15, CUL3, BTBD1 and LTN1 may play essential roles in IPAH. Predicted miRNA hsa-mir-1-3p could regulate gene expression in IPAH. Such hub genes may contribute to the pathology and progression in IPAH, providing potential diagnostic and therapeutic opportunities for IPAH patients.