Long non-coding RNA XIST promotes TGF-β-induced epithelial-mesenchymal transition by regulating miR-367/141-ZEB2 axis in non-small-cell lung cancer

• Published in: Cancer letters 2018-04, Vol.418, p.185-195
• Main Authors: Li, Chang, Wan, Liang, Liu, Zeyi, Xu, Guangquan, Wang, Shengjie, Su, Zhiyue, Zhang, Yingxi, Zhang, Cuijuan, Liu, Xia, Lei, Zhe, Zhang, Hong-Tao
• Format: Article
• Language: English
• Subjects: Animal tissues; Cell adhesion & migration; Cell migration; EMT; Gene expression; lncRNA XIST; Lung cancer; Mesenchyme; Metastases; Metastasis; MicroRNAs; miR-141; mRNA; Non-coding RNA; Non-small cell lung carcinoma; Non-small-cell lung cancer (NSCLC); Transforming growth factor; Transforming growth factor beta (TGF-β); Transforming growth factor-b; Tumors
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2018.01.036

Growing evidence shows that lncRNA XIST functions as an oncogene accelerating tumor progression. Transforming growth factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT) plays a key role in tumor metastasis. However, it is still unclear whether lncRNA XIST is implicated in TGF-β-induced EMT and influences cell invasion and metastasis in non-small-cell lung cancer (NSCLC). Here, we observed increased expression of lncRNA XIST and ZEB2 mRNA in metastatic NSCLC tissues. Knockdown of lncRNA XIST inhibited ZEB2 expression, and repressed TGF-β-induced EMT and NSCLC cell migration and invasion. Being in consistent with the in vitro findings, the in vivo experiment of metastasis showed that knockdown of lncRNA XIST inhibited pulmonary metastasis of NSCLC cells in mice. In addition, knockdown of ZEB2 expression can inhibit TGF-β-induced EMT and NSCLC cell migration and invasion. Mechanistically, lncRNA XIST and ZEB2 were targets of miR-367 and miR-141. Furthermore, both miR-367 and miR-141 expression can be upregulated by knockdown of lncRNA XIST. Taken together, our study reveals that lncRNA XIST can promote TGF-β-induced EMT and cell invasion and metastasis by regulating miR-367/miR-141-ZEB2 axis in NSCLC. •LncRNA XIST is upregulated in metastatic NSCLC tissues.•Both lncRNA XIST and ZEB2 are targets of miR-367 and miR-141.•LncRNA XIST knockdown elevates miR-367/141 expression, inhibiting ZEB2 expression and TGF-β-induced EMT in NSCLC cells.•Knockdown of lncRNA XIST inhibits pulmonary metastasis of NSCLC cells in mice.