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

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


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.

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