Regulation of activating protein-4-associated metastases of non-small cell lung cancer cells by miR-144.

Activating protein-4 (AP4) has been recently shown to regulate the cancer metastases in some cancers including non-small cell lung cancer (NSCLC). Specifically, AP4 regulates mTor/p21 and transforming growth factor β (TGFβ) receptor signaling pathway to increase an epithelial-mesenchymal transition process to augment cell invasiveness. Nevertheless, how AP4 is regulated in NSCLC has not been studied. Here, we showed that in the specimens from the NSCLC patients, the levels of miR-144 were significantly decreased and the levels of AP4 were significantly increased, compared to the paired non-tumor lung tissue. The levels of miR-144 and AP4 inversely correlated in patients' specimens. Bioinformatics analyses revealed that miR-144 targeted the 3'-UTR of AP4 mRNA to inhibit its translation, confirmed by luciferase-reporter assay. Moreover, miR-144 overexpression inhibited AP4-mediated cell invasiveness, while miR-144 depletion increased AP4-mediated cell invasiveness in NSCLC cells. Together, our data suggest that miR-144 suppression may be the cause of the increased levels of AP4, as well as the augmented cancer metastases, in NSCLC.