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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, 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??1, hypoxia?inducible factor?1, Wnt, Janus kinase, Rho?associated protein kinase, vascular endothelial growth factor, mitogen?activated protein kinase, Hedgehog and nuclear factor ?B 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.

SUBMITTER: Li R

PROVIDER: S-EPMC6202105 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Potential regulatory role of circular RNA in idiopathic pulmonary fibrosis.

Li Rongrong R Wang Youlei Y Song Xiaodong X Sun Wenjing W Zhang Jinjin J Liu Yuxia Y Li Hongbo H Meng Chao C Zhang Jie J Zheng Qingyin Q Lv Changjun C

International journal of molecular medicine 20180924 6

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 thes ...[more]

PMID: 30272257

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Project description:ObjectiveTo develop a putative microRNA (miRNA) and messenger RNA (mRNA) regulatory network of Danggui Buxue decoction's (DGBXD) amelioration of idiopathic pulmonary fibrosis (IPF).MethodsThe Gene Expression Omnibus (GEO) database was used to identify differentially expressed miRNAs (DE-miRNAs) and differentially expressed mRNAs (DE-mRNAs). Using miRNet, the predicted target genes of identified DE-miRNAs were estimated, and then the target genes of DE-miRNAs in IPF were comprehensively examined. The Enrichr database was used to conduct functional enrichment and pathway enrichment. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was employed to obtain the target genes of DGBXD as well as active compounds. A putative miRNA-mRNA regulatory network of DGBXD acting on IPF was developed by intersecting the target genes of DGBXD with the DE-miRNA target genes in IPF. A bleomycin-induced mouse model was established and used to perform histopathology as well as real-time quantitative polymerase chain reaction (qRT-PCR) analyses of some miRNA-mRNA pairs.ResultsFourteen upmodulated DE-miRNAs and six downmodulated DE-miRNAs were screened. The downstream target genes of upmodulated and downmodulated DE-miRNAs were predicted. Subsequently, 1160 upmodulated DE-mRNAs and 1427 downmodulated DE-mRNAs were identified. Then, target genes of DE-miRNAs comprising 49 downmodulated and 53 upmodulated target genes were further screened to perform functional enrichment and pathway enrichment analyses. Subsequently, 196 target genes of DGBXD were obtained from TCMSP, with six downregulated target genes and six upregulated target genes of DGBXD acting on IPF being identified. A promising miRNA-mRNA regulatory network of DGBXD acting on IPF was developed in this study. Moreover, mir-493 together with its target gene Olr1 and mir-338 together with Hif1a were further validated by qRT-PCR.ConclusionThis study proposed detailed possible processes of miRNA-mRNA modulatory axis in IPF and constructed a prospective IPF-related miRNA-mRNA modulatory network with the aim of alleviating IPF with DGBXD.

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Potential regulatory role of circular RNA in idiopathic pulmonary fibrosis.

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Potential regulatory role of circular RNA in idiopathic pulmonary fibrosis.

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