MicroRNA let-7c inhibits migration and invasion of human non-small cell lung cancer by targeting ITGB3 and MAP4K3

MicroRNAs play an important regulatory role in carcinogenesis and cancer metastasis. Different members of let-7 family have been reported to be decreased in human lung tumors. However, the effect of specific let-7 member on metastasis of NSCLC remains undefined. Our current study detected the expression of let-7 members in 94 cases of NSCLC and a significant association was noticed between low levels of let-7c expression and metastasis, venous invasion, advanced TNM stages and poor survival of NSCLC patients. Consistently, ectopic expression of let-7c in relatively highly metastatic cells remarkably suppressed their migration and invasion. Inhibition of let-7c in cells with relatively low metastatic potential promoted their motility and invasion. We then analyzed the potential targets of let-7c and found that ITGB3 and MAP4K3 were directly repressed by let-7c. Upon restoring the expression of ITGB3 and MAP4K3, the effects of let-7c on tumor metastasis were partially reversed, and more importantly, the expression levels of ITGB3 and MAP4K3 were inversely correlated with let-7c in 64 NSCLC tissues. Collectively, our results suggest that let-7c, by degrading ITGB3 and MAP4K3, prevents NSCLC metastasis.