Discovery and validation of extracellular/circulating microRNAs during idiopathic pulmonary fibrosis disease progression

Gene
Guanghai YangZhongping Xu

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial lung disease of unknown etiology that is currently untreatable. In this study we aim to characterize the potential of extracellular/circulating microRNAs (miRNAs) in serum as biomarkers for IPF. Total serum RNAs were isolated from serum from healthy control subjects (n=12), rapid progressive (n=12) and slowly progressive IPF patients (n=12). Serum RNA was analyzed by using TaqMan microRNA assays containing probes for 366 human miRNAs, and selected findings were validated with quantitative RT-PCR. Target prediction and pathway analysis on the significant differential miRNAs were performed using DIANA-mirPath. We found 47 significantly differentially expressed serum miRNAs (p<0.05) in rapid progressive or slowly progressive IPF patients compared to healthy controls, including 21 up-regulated miRNAs and 26 down-regulated miRNAs. Bioinformatic analysis by DIANA-mirPath demonstrated that 53 KEGG biological processes were significantly enriched (p < 0.05, FDR corrected) among differentially expressed serum miRNAs, including TGF-beta signaling pathway (p < 0.0001), MAPK signaling pathway (p < 0.0001), PI3K-Akt signaling pathway (p < 0.0001), Wnt signaling pathway ...Continue Reading

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