Integrative Analysis of miRNA-mRNA Networks in Idiopathic Pulmonary Fibrosis by Bioinformatics Analysis

Abstract

Purpose: To identify key biomarkers associated with the diagnosis, prognosis, and treatment of idiopathic pulmonary fibrosis (IPF), as well as to establish miRNA-mRNA regulatory networks in this disease. Methods: Differentially expressed microRNAs (DEMs) and differentially expressed genes (DEGs) were identified from the publicly-available microarray datasets GSE27430, GSE32537, and GSE24206. The transcription factors and target genes of DEMs were further predicted by FunRich and miRNet respectively. The miRNA-mRNA regulatory networks were constructed by overlapping identified target genes for DEMs and DEGs, and the output was depicted using Cytoscape software. The Gene Ontology (GO) functional annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted using OmicShare tools and R software. Results: 16 DEMs and 120 DEGs were identified within the GSE27430, GSE32537, and GSE24206 datasets. miRNA-mRNA regulatory networks were constructed with 28 miRNA gene pairs, consisting of 11 miRNAs (hsa-mir-154-5p, hsa-mir-382-5p, hsa-mir-410, hsa-mir-432-5p, hsa-mir-299-5p, hsa-mir-493-5p, hsa-mir-127-3p, hsa-mir-409-3p, hsa-mir-487b, hsa-mir-203a-3p, and hsa-mir-375) and 22 genes (C12orf75, CCDC113, CD24, GXYLT2, IL13RA2, KLHL13, MXRA5, PSD3, SPATA18, ST6GALNAC1, VCAM1, MNS1, OGN, ACSL1, ADM, HHIP, MATN3, NECAB1, PTX3, SERPINE1, SULT1B1, and THBS1). GO and KEGG analysis showed most candidate genes were enriched in pathways associated with the extracellular matrix, collagen, and platelet function. Conclusions: In this study, the miRNA-mRNA regulatory networks with 11 miRNAs and 22 mRNAs provide potential biomarkers, and may highlight novel strategies for diagnosis and treatment in IPF.