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Lung cancer is a serious threat to human health. Studies have revealed that human manganese superoxide dismutase (hSOD2) and miRNAs play an essential role in the metastasis process of lung cancer. However, the miRNAs that associated with hSOD2 and involved in metastasis, remain elusive. After databases analysis and dual luciferase reporter validation, we demonstrated that miR-330-3p expression inversely correlated with hSOD2b expression level, and that miR-330-3p directly targeted the 3'untranslated region (3'UTR) of hSOD2b. Furthermore, overexpression of miR-330-3p promoted whereas knockdown of miR-330-3p inhibited invasion/migration and the epithelial-mesenchymal transition (EMT) process of lung cancer cells in vitro. Knockdown of miR-330-3p inhibited metastasis of lung cancer cells in vivo. Moreover, miR-330-3p-mediated enhancement of invasion/migration in 95-D cells could be rescued by over-expression of hSOD2. In conclusion, we demonstrated that miR-330-3p promoted metastasis of lung cancer cells by suppressing hSOD2b expression and unveiled a new clinical application of miR-330-3p in the therapy of lung cancer.

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