Underlying Molecular Mechanism and Construction of a miRNA-Gene Network in Idiopathic Pulmonary Fibrosis by Bioinformatics

Shuping Zheng; Yan Zhang; Yangfan Hou; Hongxin Li; Jin He; Hongyan Zhao; Xiuzhen Sun; Yun Liu

doi:10.3390/ijms241713305

Underlying Molecular Mechanism and Construction of a miRNA-Gene Network in Idiopathic Pulmonary Fibrosis by Bioinformatics

Int J Mol Sci. 2023 Aug 27;24(17):13305. doi: 10.3390/ijms241713305.

Authors

Shuping Zheng¹, Yan Zhang¹, Yangfan Hou¹, Hongxin Li¹, Jin He¹, Hongyan Zhao¹, Xiuzhen Sun¹, Yun Liu¹

Affiliation

¹ Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease, but its pathogenesis is still unclear. Bioinformatics methods were used to explore the differentially expressed genes (DEGs) and to elucidate the pathogenesis of IPF at the genetic level. The microarray datasets GSE110147 and GSE53845 were downloaded from the Gene Expression Omnibus (GEO) database and analyzed using GEO2R to obtain the DEGs. The DEGs were further analyzed for Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) pathway enrichment using the DAVID database. Then, using the STRING database and Cytoscape, a protein-protein interaction (PPI) network was created and the hub genes were selected. In addition, lung tissue from a mouse model was validated. Lastly, the network between the target microRNAs (miRNAs) and the hub genes was constructed with NetworkAnalyst. A summary of 240 genes were identified as DEGs, and functional analysis highlighted their role in cell adhesion molecules and ECM-receptor interactions in IPF. In addition, eight hub genes were selected. Four of these hub genes (VCAM1, CDH2, SPP1, and POSTN) were screened for animal validation. The IHC and RT-qPCR of lung tissue from a mouse model confirmed the results above. Then, miR-181b-5p, miR-4262, and miR-155-5p were predicted as possible key miRNAs. Eight hub genes may play a key role in the development of IPF. Four of the hub genes were validated in animal experiments. MiR-181b-5p, miR-4262, and miR-155-5p may be involved in the pathophysiological processes of IPF by interacting with hub genes.

Keywords: bioinformatics; differentially expressed genes (DEGs); idiopathic pulmonary fibrosis (IPF); miRNAs (microRNAs).

MeSH terms

Animals
Computational Biology
Disease Models, Animal
Gene Regulatory Networks
Idiopathic Pulmonary Fibrosis* / genetics
Mice
MicroRNAs* / genetics
Protein Interaction Maps / genetics

Substances

MicroRNAs

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 81770037) (Y.L.), Shaanxi Provincial Natural Science Foundation Project (No. 2017JM8063) (Y.L.). The sponsor had no role in the design or conduct of this research.