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

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1864

Article

Liu, Yi¹  Li, Yan¹  Xu, Qi¹  Yao, Wenxi¹  Wu, Qiuyun¹  Yuan, Jiali¹  Yan, Weiwen¹  Xu, Tiantian¹  Ji, Xiaoming¹  Ni, Chunhui¹ 

[1] Nanjing Med Univ, Sch Publ Hlth, Dept Occupat Med & Environm Hlth, Key Lab Modern Toxicol,Minist Educ, Nanjing 211166, Jiangsu, Peoples R China

关键词: lncRNA-ATB;    miR-200c;    EMT;    Macrophages;    Silicosis;   

DOI  :  10.1016/j.bbadis.2017.11.003

来源: Elsevier

【 摘 要 】

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-beta 1 (TGF-beta 1) to induce EMT process by activating lncRNA-ATB in epithelial cells. Collectively, silica-stimulated macrophages secreted TGF-beta 1 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.

【 授权许可】

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