Soochow University Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou, Jiangsu, 215123, China; Department of Genetics, School of Biology and Basic Medical Science, Medical College of Soochow University, Suzhou, Jiangsu, 215123, China; Department of Cardiothoracic Surgery, The First Affiliated Hospital of Soochow University, Medical College of Soochow University, Suzhou, Jiangsu, 215006, China.
Soochow University Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou, Jiangsu, 215123, China; Department of Genetics, School of Biology and Basic Medical Science, Medical College of Soochow University, Suzhou, Jiangsu, 215123, China.
Cancer Lett. 2018 Apr 1;418:185-195. doi: 10.1016/j.canlet.2018.01.036. Epub 2018 Jan 17.
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.
越来越多的证据表明，lncRNA XIST 作为一种癌基因，加速肿瘤的进展。转化生长因子β（TGF-β）诱导的上皮-间充质转化（EMT）在肿瘤转移中起着关键作用。然而，lncRNA XIST 是否参与 TGF-β诱导的 EMT 以及是否影响非小细胞肺癌（NSCLC）中的细胞侵袭和转移仍不清楚。在这里，我们观察到转移性 NSCLC 组织中 lncRNA XIST 和 ZEB2 mRNA 的表达增加。lncRNA XIST 的敲低抑制了 ZEB2 的表达，并抑制了 TGF-β诱导的 EMT 和 NSCLC 细胞迁移和侵袭。与体外研究结果一致，体内转移实验表明，lncRNA XIST 的敲低抑制了小鼠 NSCLC 细胞的肺转移。此外，敲低 ZEB2 的表达可以抑制 TGF-β诱导的 EMT 和 NSCLC 细胞迁移和侵袭。机制上，lncRNA XIST 和 ZEB2 是 miR-367 和 miR-141 的靶标。此外，lncRNA XIST 的敲低可以上调 miR-367 和 miR-141 的表达。综上所述，我们的研究表明，lncRNA XIST 通过调节 miR-367/miR-141-ZEB2 轴促进 TGF-β 诱导的 EMT 和 NSCLC 细胞的侵袭和转移。
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