LncRNA PFAR contributes to fibrogenesis in lung fibroblasts through competitively binding to miR-15a

• Published in: Bioscience reports 2019-07, Vol.39 (7)
• Main Authors: Sun, Jian, Su, Wei, Zhao, Xiaoguang, Shan, Tianjiao, Jin, Tongzhu, Guo, Yingying, Li, Chao, Li, Ruotong, Zhou, Yuhong, Shan, Hongli, Sun, Xiaohan, Liang, Haihai
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Base Pairing; Base Sequence; Bleomycin - administration & dosage; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Differentiation; Cell Movement; Cell Proliferation; Collagen Type I - genetics; Collagen Type I - metabolism; Disease Models, Animal; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - pathology; Gene Expression Regulation; Humans; Idiopathic Pulmonary Fibrosis - chemically induced; Idiopathic Pulmonary Fibrosis - genetics; Idiopathic Pulmonary Fibrosis - metabolism; Idiopathic Pulmonary Fibrosis - pathology; Lung - drug effects; Lung - metabolism; Lung - pathology; Male; Mice; Mice, Inbred C57BL; MicroRNAs - genetics; MicroRNAs - metabolism; Primary Cell Culture; RNA, Long Noncoding - antagonists & inhibitors; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Signal Transduction; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism; Twist-Related Protein 1 - genetics; Twist-Related Protein 1 - metabolism
• ISSN: 0144-8463; 1573-4935
• DOI: 10.1042/BSR20190280

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, debilitating disease with unknown etiopathogenesis. Previous reports have reported that long non-coding RNAs (lncRNAs) were involved in various pathophysiological processes. However, the role of lncRNAs in IPF has not been fully described. We aimed to explore the relationship between miR-15a and lncRNA PFAR and its function in pulmonary fibrosis. Biological information analysis and luciferase were used to identify targeted binding of lncRNA PFAR and miR-15a. Western blot, quantitative reverse transcription-PCR (qRT-PCR) and immunofluorescence staining were conducted to detect fibrosis-related factors. Fibroblasts proliferation were analyzed using 5-ethynyl-2'-deoxyuridine (EdU) staining and fibroblasts migration ability were measured using wound-healing scratch assay. We identified that lncRNA PFAR has a binding site with miR-15a and luciferase reporter assays demonstrated their combinative relationship. Our results showed that silencing PFAR attenuated TGF-β1 induced fibrogenesis in primary lung fibroblasts. And miR-15a antagonized the function of PFAR and inhibited PFAR induced extracellular collagen deposition, fibroblasts proliferation, migration and differentiation. In conclusion, our results revealed that PFAR functions as a competitive endogenous RNA (ceRNA) by acting as a sponge for miR-15a, revealing a potential regulatory network involving PFAR and miR-15a with a role in the modulation of YAP1-Twist expression. This mechanism may contribute to a better understanding of pulmonary fibrosis pathogenesis and treatment method.