Abstract
This study investigated the role of miR-3188 on the proliferation of non-small cell lung cancer cells and its relationship to FOXO1-modulated feedback loop. Two non-small cell lung cancer (NSCLC) cell lines A549 and H1299 were used. RNA silencing was achieved by lentiviral transfection. Cell proliferation was assessed by immunohistochemical staining of Ki67 and PCNA, Edu incorporation, and colony formation assay. Western blotting 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-3188 reduced cell proliferation in NSCLC cells. Molecular analyses indicated that the effect of mammalian target of rapamycin (mTOR) was directly mediated by miR-3188, leading to p-PI3K/p-AKT/c-JUN inactivation. The inhibition of this signaling pathway further caused cell-cycle suppression. Moreover, FOXO1 was found to be involved in regulating the interaction 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 and FOXO1 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.
Highlights
MicroRNAs play important roles in development, cellular differentiation, proliferation, cell cycle control, and cell death (Bhaskaran and Mohan, 2014)
It was found that miR-3188 is overexpressed in non-small cell lung cancer (NSCLC) cells but its expression is low in BEAS-2B cells (Figure 1A)
These results indicate that miR-3188 is capable of inhibiting cell proliferation and inducing G1/S transition in NSCLC cells
Summary
MicroRNAs (miRNAs or miRs) play important roles in development, cellular differentiation, proliferation, cell cycle control, and cell death (Bhaskaran and Mohan, 2014). They are critical in development and progression of various kinds of diseases including cancer (Hayes et al, 2014; Rupaimoole and Slack, 2017). It has been reported that miRNAs can regulate chemotherapeutic efficacy in multiple cancers (Magee et al, 2015; Mognato and Celotti, 2015). Bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs)-derived exosomes promote colon cancer stem celllike traits via miR-142-3p, suggesting multiple ways of miRNAs in regulatiing cancer progression
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