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
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
复制标题
长非编码RNA XIST通过调节非小细胞肺癌中的miR-367/141-ZEB2轴促进TGF-β诱导的上皮间质转化
DOI：
10.1016/j.canlet.2018.01.036
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发表时间：
2018-04-01
期刊：
影响因子：
9.7
通讯作者：
Zhang, Hong-Tao
中科院分区：
文献类型：
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作者：
Li, Chang;Wan, Liang;Zhang, Hong-Tao
越来越多的证据表明，长链非编码RNA XIST作为一种癌基因发挥作用，加速肿瘤进展。转化生长因子β（TGF -β）诱导的上皮 - 间质转化（EMT）在肿瘤转移中起关键作用。然而，长链非编码RNA XIST是否参与TGF -β诱导的EMT并影响非小细胞肺癌（NSCLC）细胞的侵袭和转移仍不清楚。在此，我们观察到转移性非小细胞肺癌组织中长链非编码RNA XIST和ZEB2 mRNA的表达增加。敲低长链非编码RNA XIST可抑制ZEB2表达，并抑制TGF -β诱导的EMT以及非小细胞肺癌细胞的迁移和侵袭。与体外研究结果一致，体内转移实验表明，敲低长链非编码RNA XIST可抑制小鼠非小细胞肺癌细胞的肺转移。此外，敲低ZEB2表达可抑制TGF -β诱导的EMT以及非小细胞肺癌细胞的迁移和侵袭。从机制上讲，长链非编码RNA XIST和ZEB2是miR - 367和miR - 141的靶标。此外，敲低长链非编码RNA XIST可上调miR - 367和miR - 141的表达。综上所述，我们的研究揭示了在非小细胞肺癌中，长链非编码RNA XIST可通过调节miR - 367/miR - 141 - ZEB2轴促进TGF -β诱导的EMT以及细胞的侵袭和转移。（C）2018爱思唯尔有限公司。保留所有权利。
Growing evidence shows that IncRNA XIST functions as an oncogene accelerating tumor progression. Transforming growth factor beta (TGF-beta)-induced epithelial-mesenchymal transition (EMT) plays a key role in tumor metastasis. However, it is still unclear whether IncRNA XIST is implicated in TGF-beta-induced EMT and influences cell invasion and metastasis in non-small-cell lung cancer (NSCLC). Here, we observed increased expression of IncRNA XIST and ZEB2 mRNA in metastatic NSCLC tissues. Knockdown of IncRNA XIST inhibited ZEB2 expression, and repressed TGF-beta-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 IncRNA XIST inhibited pulmonary metastasis of NSCLC cells in mice. In addition, knockdown of ZEB2 expression can inhibit TGF-beta-induced EMT and NSCLC cell migration and invasion. Mechanistically, IncRNA 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 IncRNA XIST. Taken together, our study reveals that IncRNA XIST can promote TGF-beta-induced EMT and cell invasion and metastasis by regulating miR-367/miR-141-ZEB2 axis in NSCLC. (C) 2018 Elsevier B.V. All rights reserved.