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

Autor: Yingying Guo, Hongli Shan, Xiaohan Sun, Chao Li, Jian Sun, Yuhong Zhou, Xiaoguang Zhao, Tongzhu Jin, Haihai Liang, Ruotong Li, Wei Su, Tianjiao Shan
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Cell Cycle Proteins
Biochemistry
Pathogenesis
Idiopathic pulmonary fibrosis
Mice
0302 clinical medicine
Cell Movement
Pulmonary fibrosis
RNA
Small Interfering
Base Pairing
Lung
Research Articles
medicine.diagnostic_test
microRNA
Chemistry
Cell Differentiation
large intervening non-coding RNA
030220 oncology & carcinogenesis
RNA
Long Noncoding
Signal Transduction
Research Article
Primary Cell Culture
Biophysics
Collagen Type I
Transforming Growth Factor beta1
03 medical and health sciences
Bleomycin
Western blot
fibroblasts
medicine
Gene silencing
Animals
Humans
Luciferase
Molecular Biology
Adaptor Proteins
Signal Transducing
Cell Proliferation
Base Sequence
Competing endogenous RNA
Twist-Related Protein 1
YAP-Signaling Proteins
Cell Biology
medicine.disease
Idiopathic Pulmonary Fibrosis
Collagen Type I
alpha 1 Chain
Mice
Inbred C57BL
Disease Models
Animal
MicroRNAs
030104 developmental biology
Gene Expression Regulation
Cancer research
Zdroj: Bioscience Reports
ISSN: 1573-4935
Popis: 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.
Databáze: OpenAIRE
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