Journal
ONCOTARGET
Volume 6, Issue 10, Pages 8244-8254Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3135
Keywords
NSCLC; miR-124; MYO10; NF-kappa B; metastasis
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Recently, dysregulation of microRNAs plays a critical role in cancer metastasis. Here, an in vivo selection approach was used to generate highly aggressive NSCLC sub-cell lines followed by comparing the microRNAs expression using microarrays. miR-124 was notably deregulated in both highly invasive sub-cell lines and nodepositive NSCLC specimens. Over-expression of miR-124 robustly attenuated migration and metastatic ability of the aggressive cells. MYO10 was subsequently identified as a novel functional downstream target of miR-124, and was up-regulated in nodepositive NSCLC tissues. Knockdown of MYO10 inhibited cell migration, whereas forced MYO10 expression markedly rescued miR-124-mediated suppression of cell metastasis. Additionally, we found an activated NF-kappa B-centered inflammatory loop in the highly aggressive cells leading to down-regulation of miR-124. These results suggest that NF-kappa B-regulated miR-124 targets MYO10, inhibits cell invasion and metastasis, and is down-regulated in node-positive NSCLC.
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