NF-κB-mediated miR-124 suppresses metastasis of non-small-cell lung cancer by targeting MYO10

// Yingjia Sun 1 , Xinghao Ai 1 , Shengping Shen 1 , Shun Lu 1 1 Lung Tumor Clinical Medical Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China Correspondence to: Shun Lu, e-mail: shunlu2020@163.com Keywords: NSCLC, miR-124, MYO10, NF-κB, metastasis Received: October 18, 2014      Accepted: January 10, 2015      Published: January 29, 2015 ABSTRACT 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 node-positive 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 node-positive 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-κB-centered inflammatory loop in the highly aggressive cells leading to down-regulation of miR-124. These results suggest that NF-κB-regulated miR-124 targets MYO10, inhibits cell invasion and metastasis, and is down-regulated in node-positive NSCLC.