Long non-coding RNA-ATB promotes EMT during silica-induced pulmonary fibrosis by competitively binding miR-200c

• Published in: Biochimica et biophysica acta. Molecular basis of disease Vol. 1864; no. 2; pp. 420 - 431
• Main Authors: Liu, Yi, Li, Yan, Xu, Qi, Yao, Wenxi, Wu, Qiuyun, Yuan, Jiali, Yan, Weiwen, Xu, Tiantian, Ji, Xiaoming, Ni, Chunhui
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2018
• Subjects: A549 Cells; Animals; Cell Proliferation; Coculture Techniques; EMT; Epithelial Cells - metabolism; Epithelial-Mesenchymal Transition - genetics; Humans; lncRNA-ATB; Lung - metabolism; Macrophages; Macrophages - metabolism; Male; Mice; Mice, Inbred C57BL; MicroRNAs - metabolism; miR-200c; Oligonucleotide Array Sequence Analysis; Protein Binding; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - pathology; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Signal Transduction; Silicon Dioxide - toxicity; Silicosis; Transfection; Transforming Growth Factor beta1 - metabolism; Wound Healing; Zinc Finger E-box-Binding Homeobox 1 - metabolism; lncRNA-ATB; Macrophages; miR-200c; EMT; Silicosis
• ISSN: 0925-4439; 1879-260X
• DOI: 10.1016/j.bbadis.2017.11.003

Long non-coding RNAs (lncRNAs) are important signal transduction regulators that act by various patterns. However, little is known about the molecular mechanisms of lncRNA related pathways in occupational lung fibrosis. Our previous study found that epithelial-mesenchymal transition (EMT) was one of the key events in silica-induced pulmonary fibrosis. This study showed that the lncRNA-ATB promoted EMT by acting as a miR-200c sponge. miR-200c was identified by miRNA array as a potential target of lncRNA-ATB and verified by dual luciferase reporter gene together with RNA pull-down assays. Moreover, our findings demonstrated that lncRNA-ATB is abundantly expressed during EMT of lung epithelial cells, which contributes to decreased levels of miR-200c. miR-200c targeted ZEB1 to relief silicosis by blocking EMT in vivo and in vitro. The results also suggested M2 macrophages secreted transforming growth factor-β1 (TGF-β1) to induce EMT process by activating lncRNA-ATB in epithelial cells. Collectively, silica-stimulated macrophages secreted TGF-β1 to induce lncRNA-ATB in epithelia cells, promoting EMT by binding with miR-200c and releasing ZEB1. These observations provide further understanding of the regulatory network of silica-induced pulmonary fibrosis and identify new therapeutic targets hopefully. •Silica stimulated macrophages secrete TGF-β1 to induce lncRNA-ATB in epithelia cells.•LncRNA-ATB binds with miR-200c to relieve ZEB1 causing accelerated EMT process.•CeRNA mechanism is involved in EMT during silica-induced pulmonary fibrosis.