This study investigated the role of miR-3188 on the proliferation of non-small cell lungcancer cells and its relationship to FOXO1-modulated feedback loop. Two non-small celllung cancer (NSCLC) cell lines A549 and H1299 were used. RNA silencing was achievedby lentiviral transfection. Cell proliferation was assessed by immunohistochemical staining of Ki67 and PCNA, Edu incorporation, and colony formation assay. Westernblotting was used to examine expression of FOXO1, mTOR, p-mTOR, CCND1, p21,c-JUN, AKT, pAKT, PI3K, p-PI3K, and p27 proteins. It was found that miR-3188reduced cell proliferation in NSCLC cells. Molecular analyses indicated that the effect of
mammalian target of rapamycin (mTOR) was directly mediated by miR-3188, leading top-PI3K/p-AKT/c-JUN inactivation. The inhibition of this signaling pathway further causedcell-cycle suppression. Moreover, FOXO1 was found to be involved in regulating theinteraction of miR-3188 and mTOR through p-PI3K/p-AKT/c-JUN signaling pathway.Taken together, our study demonstrated that miR-3188 interacts with mTOR andFOXO1 to inhibit NSCLC cell proliferation through a mTOR-p-PI3K/AKT-c-JUN signaling pathway. Therefore, miR-3188 might be a potential target for the treatment of NSCLC.
Keywords: miR-3188, NSCLC, proliferation, mTOR, PI3K/AKT, c-J