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miR-363-3p 通过靶向非小细胞肺癌中的 NEDD9 和 SOX4 抑制迁移、侵袭和上皮-间充质转化。

miR-363-3p inhibits migration, invasion, and epithelial-mesenchymal transition by targeting NEDD9 and SOX4 in non-small-cell lung cancer.

机构信息

Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Physiology, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania.

出版信息

J Cell Physiol. 2020 Feb;235(2):1808-1820. doi: 10.1002/jcp.29099. Epub 2019 Jul 22.

Abstract

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.

摘要

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。

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