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  • Title: Mechanism of LncRNA XIST/ miR-101-3p/ZEB1 axis in EMT associated with silicosis.
    Author: Li C, Xia J, Yao W, Yang G, Tian Y, Qi Y, Hao C.
    Journal: Toxicol Lett; 2022 May 01; 360():11-19. PubMed ID: 35271943.
    Abstract:
    Silicosis is a systemic disease characterized by diffuse fibrosis of lung tissue. However, its pathogenesis has not been fully elucidated. Previous studies have demonstrated that there is a close relationship between EMT and pulmonary fibrosis. However, LncRNA XIST and miR-101-3p regulate the expression of ZEB1 which is a key transcription factor in the process of EMT through competitive endogenous RNA, thus affecting the process of EMT has not been reported. In this work, an experimental silicosis mouse model and cell model of TGF-β1 stimulated lung epithelial cells (A549) for 48 h are established to investigate the biological effects of LncRNA XIST/ miR-101-3p/ZEB1 axis in the EMT process. The results reveal that LncRNA XIST and ZEB1 are up-regulated while the miR-101-3p expression is down-regulated in vivo and vitro models. Furthermore, the knockdown of LncRNA XIST prevents the EMT process and the inhibition of miR-101-3p markedly promotes EMT stimulated by TGF-β1. Moreover, the results also illustrate that LncRNA XIST is mainly localized in the cytoplasm used FISH and possesses binding site with miR-101-3p which was identified as the target of ZEB1 used bioinformatics prediction website and Dual-luciferase reporter assay. The above demonstrated that LncRNA-XIST regulates ZEB1 by directly sponging miR-101-3p. To sum up, we uncovered that the up-regulated LncRNA XIST can modulate miR-101-3p and then up-regulate the expression of ZEB1, thus promoting the EMT process of alveolar epithelial cells in the process of silicosis-related pulmonary fibrosis EMT. Our study provides a new research idea for related targets of silicosis treatment.
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