XB130, regulated by miR-203, miR-219, and miR-4782-3p, mediates the proliferation and metastasis of non-small-cell lung cancer cells
XB130, regulated by miR-203, miR-219, and miR-4782-3p, mediates the proliferation and metastasis of non-small-cell lung cancer cells
复制标题
XB130受miR-203、miR-219和miR-4782-3p调控，介导非小细胞肺癌细胞的增殖和转移
DOI：
10.1002/mc.23180
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发表时间：
2020-05-01
影响因子：
4.6
通讯作者：
Zhou, Jianjiang
中科院分区：
文献类型：
--
作者：
Wang, Qinrong;Yang, Guohui;Zhou, Jianjiang
XB130是一种新型的适配器蛋白，在不同人类肿瘤的发展中作为肿瘤启动子或抑制子介导细胞增殖和转移。XB130在人非小细胞肺癌（NSCLC）中表达改变已得到证实。然而，XB130对NSCLC的确切作用尚不清楚。在这项研究中，我们研究了XB130在NSCLC中的生物学功能和转录后调控。首先，研究了XB130沉默对NSCLC细胞增殖、迁移、侵袭和上皮-间质转化（EMT）的影响。然后通过双荧光素酶报告基因检测证实XB130与miR-203、miR-219或miR-4782-3p之间的靶向关系。最后，我们分别研究了miR-203、miR-219和miR-4782-3p对NSCLC细胞功能的影响。我们发现XB130沉默显著抑制细胞生长、迁移和侵袭，逆转EMT。此外，XB130受miR-203、miR-219和miR-4782-3p的转录后调控。过表达miR-203、miR-219或miR-4782-3p可抑制细胞生长、迁移和侵袭，逆转EMT，其作用与XB130在NSCLC细胞中的作用相同，而过表达microRNA （miRNA）的抑制作用被miRNA抑制剂或XB130在NSCLC细胞中的异位表达所削弱。这些数据表明，XB130受miR-203、miR-219和miR-4782-3p的转录后调控，并介导NSCLC细胞的增殖和转移。
XB130 is a novel adapter protein that behaves as a tumor promoter or suppressor mediating cell proliferation and metastasis in the development of different human tumors. Altered expression of XB130 has been verified in human non-small cell-lung cancer (NSCLC). However, the exact effect of XB130 on NSCLC is not well-understood. In this study, we investigated the biological function and posttranscriptional regulation of XB130 in NSCLC. First, the effects of XB130 silence on NSCLC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) were examined. Then the targeting relationship between XB130 and miR-203, miR-219, or miR-4782-3p was demonstrated by dual-luciferase reporter assay. Finally, the effects of miR-203, miR-219, and miR-4782-3p on NSCLC cell function were studied, respectively. We found that XB130 silence significantly inhibited cell growth, migration and invasion, and reversed EMT. Furthermore, XB130 was posttranscriptionally regulated by miR-203, miR-219, and miR-4782-3p. Overexpression of miR-203, miR-219, or miR-4782-3p inhibited cell growth, migration and invasion, and reversed EMT, just like the role of XB130 in NSCLC cells, whereas the suppressive effects of microRNA (miRNA) overexpression were weakened by miRNA inhibitors or ectopic expression of XB130 in NSCLC cells. These data demonstrate that XB130 is posttranscriptionally regulated by miR-203, miR-219, and miR-4782-3p and mediates the proliferation and metastasis of NSCLC cells.