Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Physiology, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania.
J Cell Physiol. 2020 Feb;235(2):1808-1820. doi: 10.1002/jcp.29099. Epub 2019 Jul 22.
miR-363-3p is downregulated in lung adenocarcinoma and can inhibit tumor growth. Here, we aimed to investigate the effect of miR-363-3p on non-small-cell lung cancer (NSCLC) metastasis. In our study, miR-363-3p overexpression inhibited cell migration and invasion via epithelial-mesenchymal transition inhibition, while miR-363-3p knockdown exhibited the opposite effects. Further studies demonstrated that miR-363-3p bound to 3'-untranslated regions of NEDD9 and SOX4, and negatively regulated their levels. Interestingly, NEDD9 or SOX4 knockdown rescued the metastasis-promoting effects of antagomiR-363-3p. The inhibitory effects of agomiR-363-3p were also blocked by NEDD9 or SOX4 overexpression. Moreover, lentivirus particles carrying pre-miR-363 (LV-pre-miR-363) significantly decreased, while LV-miR-363-3p inhibitor increased metastatic nodule numbers and the levels of NEDD9 and SOX4 in lungs. In conclusion, tumor suppressor miR-363-3p may be a potential target in NSCLC therapy.
miR-363-3p 在肺腺癌中下调，可抑制肿瘤生长。本研究旨在探讨 miR-363-3p 对非小细胞肺癌（NSCLC）转移的影响。研究发现，miR-363-3p 过表达通过抑制上皮-间充质转化抑制细胞迁移和侵袭，而 miR-363-3p 敲低则表现出相反的效果。进一步的研究表明，miR-363-3p 结合 NEDD9 和 SOX4 的 3'-非翻译区，并负调控其水平。有趣的是，NEDD9 或 SOX4 的敲低可挽救 antagomiR-363-3p 的促转移作用。NEDD9 或 SOX4 的过表达也阻断了 agomiR-363-3p 的抑制作用。此外，携带 pre-miR-363 的慢病毒颗粒（LV-pre-miR-363）显著减少，而 LV-miR-363-3p 抑制剂则增加肺部转移结节数量和 NEDD9 和 SOX4 的水平。综上所述，肿瘤抑制 miR-363-3p 可能是 NSCLC 治疗的一个潜在靶点。
