Increasing evidence reveals that deregulation of miRNAs contributes to carcinogenesis of the human non-small cell lung cancer (NSCLC). Our study discovered that the expression of miR-449a was markedly decreased in NSCLC cells with high metastatic capacity and tissues of positive lymph node metastasis. Moreover, our results showed that miR-449a could act as a tumor suppressor by inhibiting the invasion of NSCLC cells in vitro and in vivo. Mechanistically, miR-449a inhibited the expression of MAP2K1 by direct targeting its 3'UTR, and regulated the activity of MEK1/ERK1/2/c-Jun pathway through an auto-regulatory feedback loop. Furthermore, the histone methylation mediated the decreased expression of miR-449a through SUZ12. Taken together, the novel connection between miR-449a and MAP2K1 demonstrated here provided a new, potential therapeutic target for the treatment of non-small cell lung cancer.
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