Potential regulatory role of circular RNA in idiopathic pulmonary fibrosis

Li,Rongrong; Wang,Youlei; Song,Xiaodong; Sun,Wenjing; Zhang,Jinjin; Liu,Yuxia; Li,Hongbo; Meng,Chao; Zhang,Jie; Zheng,Qingyin; Lv,Changjun

doi:10.3892/ijmm.2018.3892

Potential regulatory role of circular RNA in idiopathic pulmonary fibrosis

Authors:
- Rongrong Li
- Youlei Wang
- Xiaodong Song
- Wenjing Sun
- Jinjin Zhang
- Yuxia Liu
- Hongbo Li
- Chao Meng
- Jie Zhang
- Qingyin Zheng
- Changjun Lv
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Affiliations: Department of Respiratory Medicine, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong 256602, P.R. China, School of Special Education, Binzhou Medical University, Yantai, Shandong 264003, P.R. China, School of Pharmacy, Binzhou Medical University, Yantai, Shandong 264003, P.R. China, School of Life Sciences, Ludong University, Yantai, Shandong 264025, P.R. China
Published online on: September 24, 2018 https://doi.org/10.3892/ijmm.2018.3892
Pages: 3256-3268
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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, hsa_circRNA_102100 and hsa_circRNA_102348 were significantly upregulated, whereas hsa_circRNA_101225, hsa_circRNA_104780 and hsa_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 hsa_circRNA_100906 and hsa_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.

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