Key Laboratory of Endemic and Ethnic Diseases, Guizhou Medical University, Ministry of Education, Guiyang, China.
Key Laboratory of Medical Molecular Biology, Guizhou Medical University, Guiyang, China.
Mol Carcinog. 2020 May;59(5):557-568. doi: 10.1002/mc.23180. Epub 2020 Mar 11.
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.
XB130 是一种新型的衔接蛋白，作为肿瘤促进或抑制因子，在不同人类肿瘤的细胞增殖和转移中发挥作用。XB130 的表达改变已在人类非小细胞肺癌（NSCLC）中得到验证。然而，XB130 对 NSCLC 的确切影响尚不清楚。在本研究中，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-间充质转化（EMT）的影响。然后，通过双荧光素酶报告基因检测证实了 XB130 与 miR-203、miR-219 或 miR-4782-3p 的靶向关系。最后，分别研究了 miR-203、miR-219 和 miR-4782-3p 对 NSCLC 细胞功能的影响。结果发现，XB130 沉默显著抑制细胞生长、迁移和侵袭，并逆转 EMT。此外，XB130 受 miR-203、miR-219 和 miR-4782-3p 的转录后调控。miR-203、miR-219 或 miR-4782-3p 的过表达抑制细胞生长、迁移和侵袭，并逆转 EMT，就像 XB130 在 NSCLC 细胞中的作用一样，而 miRNA 抑制剂或 XB130 在 NSCLC 细胞中的异位表达则削弱了 miRNA 的抑制作用。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。
