Long non-coding RNA-ATB promotes EMT during silica-induced pulmonary fibrosis by competitively binding miR-200c.
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.
['Liu|Yi|Y|', 'Li|Yan|Y|', 'Xu|Qi|Q|', 'Yao|Wenxi|W|', 'Wu|Qiuyun|Q|', 'Yuan|Jiali|J|', 'Yan|Weiwen|W|', 'Xu|Tiantian|T|', 'Ji|Xiaoming|X|', 'Ni|Chunhui|C|']
D000072283:A549 Cells D000818:Animals D049109:Cell Proliferation D018920:Coculture Techniques D004847:Epithelial Cells D058750:Epithelial-Mesenchymal Transition D006801:Humans D008168:Lung D008264:Macrophages D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D035683:MicroRNAs D020411:Oligonucleotide Array Sequence Analysis D011485:Protein Binding D011658:Pulmonary Fibrosis D062085:RNA, Long Noncoding D015398:Signal Transduction D012822:Silicon Dioxide D014162:Transfection D053773:Transforming Growth Factor beta1 D014945:Wound Healing D000071799:Zinc Finger E-box-Binding Homeobox 1
EMT miR-200c lncRNA-ATB Silicosis Macrophages