Mir-802 Inhibits The Aggressive Behaviors Of Non-Small Cell Lung Cancer Cells By Directly Targeting Fgfr1

Emerging reports have revealed that several microRNAs (miRNAs) are abnormally expressed in non-small cell lung cancer (NSCLC). miRNAs have been identified as oncogenes or tumor suppressors, and regulate various biological processes including oncogenesis and development. miR-802 is dysregulated in multiple types of human cancer, and exerts tumor-suppressive or promoting roles. However, the expression levels and functional roles of miR-802 in NSCLC remain largely unknown. In the present study, miR-802 expression was demonstrated to be decreased in NSCLC tissues and cell lines. A low miR-802 expression was significantly correlated with the tumor stage, lymph node metastasis and brain metastasis in NSCLC patients. Restoring miR-802 expression inhibited NSCLC cell proliferation and colony formation, induced cell apoptosis, decreased cell migration and invasion in vitro, and hindered in vivo tumor growth. Mechanistically, fibroblast growth factor receptor 1 (FGFR1) was confirmed as the target gene of miR-802 in NSCLC cells. In addition, FGFR1 silencing mimicked the tumor-suppressing roles of miR-802 upregulation in NSCLC cells. Furthermore, rescue experiments revealed that FGFR1 reintroduction rescued the miR-802-induced inhibition of the malignant phenotypes in NSCLC cells. Notably, miR-802 was able to deactivate the phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase (Akt)/mammalian target of rapamycin (mTOR) pathway in NSCLC cells in vitro and in vivo. Overall, these results demonstrated that miR-802 could downregulate FGFR1 expression, thereby deactivating the PI3K/Akt/mTOR pathway and inhibiting the malignant development of NSCLC. Thus, miR-802 may be a therapeutic candidate for patients with NSCLC.