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Abstract
Long non-coding RNAs (lncRNAs) have been reported to be involved in various pathophysiological processes in many diseases. However, the role and mechanism of lncRNAs in pulmonary fibrosis have not been explicitly delineated. In the present study, we found that lncRNA ZEB1 antisense RNA 1 (ZEB1-AS1) is upregulated in the lungs of BLM-induced rats and TGF-β1-induced RLE-6TN cells, and positively correlated with the levels of ZEB1, an epithelial–mesenchymal transition (EMT) master regulator. Knockdown of ZEB1-AS1 alleviated BLM-induced fibrogenesis, in vivo, via inhibiting EMT progress. Mechanistically, we identified that ZEB1-AS1 promoted fibrogenesis in RLE-6TN cells and ZEB1-AS1 silencing inhibited TGF-β1-induced fibrogenesis through modulation of miR-141-3p. Further experiments revealed that ZEB1-AS1 acted as competing endogenous RNA (ceRNA) of miR-141-3p: forced expression of ZEB1-AS1 reduced the expression of miR-141-3p to activate Zinc-finger Ebox Binding Homeobox 1 (ZEB1) in RLE-6TN cells. In addition, we found that upregulation of miR-141-3p prevented fibrogenesis by targeting ZEB1. Therefore, our finding suggested lncRNA ZEB1-AS1 as a new profibrotic molecule that acts as a regulator of miR-141-3p/ZEB1 axis during lung fibrosis and demonstrated ZEB1-AS1 as a potential therapeutic target for the prevention and treatment of pulmonary fibrosis.
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1 Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Department of Lung Disease, Jinan, People’s Republic of China (GRID:grid.479672.9)
2 Shandong Academy of Medical Sciences, Department of Traditional Chinese Medicine, Shandong Academy of Occupational Health and Occupational Medicine, Jinan, People’s Republic of China (GRID:grid.410587.f)
3 Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Department of Endocrinology, Jinan, People’s Republic of China (GRID:grid.479672.9)
4 Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Department of Scientific Research, Jinan, People’s Republic of China (GRID:grid.479672.9)
5 Shandong University of Traditional Chinese Medicine, Department of Chinese Internal Medicine, Jinan, People’s Republic of China (GRID:grid.464402.0) (ISNI:0000 0000 9459 9325)
6 Shandong University of Traditional Chinese Medicine, First Clinical Medical College, Jinan, People’s Republic of China (GRID:grid.464402.0) (ISNI:0000 0000 9459 9325)