Potential regulatory role of circular RNA in idiopathic pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive type of interstitial pneumonia with unknown causes, poor prognosis and no effective therapy available. Circular RNAs (circRNAs), which serve as potential therapeutic targets and diagnostic biomarkers for certain diseases, represent a recent hotspot in the field of RNA research. In the present study, a total of 67 significantly dysregulated circRNAs were identified in the plasma of IPF patients by using a circRNA microarray. Among these circRNAs, 38 were upregulated, whereas 29 were downregulated. Further validation of the results by polymerase chain reaction analysis indicated that Homo sapiens (hsa)-circRNA-100906, has-circRNA-102100 and has-circRNA-102348 were significantly upregulated, whereas has-circRNA-101225, has-circRNA-104780 and has-circRNA-101242 were downregulated in plasma samples of IPF patients compared with those in samples from healthy controls. The majority of differentially expressed circRNAs were generated from exonic regions. The host genes of the differentially expressed circRNAs were involved in the regulation of the cell cycle, adherens junctions and RNA transport. The competing endogenous RNA (ceRNA) network of the circRNAs/micro(mi)RNAs/mRNAs indicated that circRNA-protected mRNA participated in transforming growth factor-β1, hypoxia-inducible factor-1, Wnt, Janus kinase, Rho-associated protein kinase, vascular endothelial growth factor, mitogen-activated protein kinase, Hedgehog and nuclear factor κB signalling pathways or functioned as biomarkers for pulmonary fibrosis. Furthermore, luciferase reporter assays confirmed that has-circRNA-100906 and has-circRNA-102348 directly interact with miR-324-5p and miR-630, respectively, which were downregulated in IPF patients. The present study provided a novel avenue for exploring the underlying molecular mechanisms of IPF disease.