MiR-4299 suppresses non-small cell lung cancer cell proliferation, migration and invasion through modulating PTEN/AKT/PI3K pathway.

OBJECTIVE: The aim of the present study was to investigate clinical significances and biological roles of miR-4299 in non-small cell lung cancer (NSCLC) PATIENTS AND METHODS: Expression of miR-4299 in NSCLC tissues and matched non-tumor tissues was determined by quantitative real-time PCR (qRT-PCR). The correlations between miR-4299 expression and clinicopathological characteristics and prognosis were also analyzed. MTT assay and Transwell assay were performed to determine the proliferation, migration and invasion. Western blotting was used to examine the expressing patterns of PTEN/AKT/PI3K signaling pathway-related proteins.

RESULTS: We found that the expression level of miR-4299 was downregulated in NSCLC tissues and cell lines. Low miR-4299 expression was positively correlated with TNM stage (p=0.002), histological grade (p=0.002) and lymph node metastasis (p=0.028). Moreover, Kaplan-Meier survival analysis showed that the patients with low miR-4299 expression had shorter survival time than those with high miR-4299 expression (p=0.0011). More importantly, multivariate analysis suggested that decreased miR-4299 expression was a poor independent prognostic predictor for NSCLC patients (p=0.009). Functionally, overexpression of miR-4299 inhibited the proliferation, migration and invasion in A549 cells. Mechanistically, the results of Western blot showed that miR-4299 exhibited its tumor-suppressive role by modulating PTEN/AKT/PI3K signaling pathway.

CONCLUSIONS: We firstly indicated that miR-4299 may be a candidate independent marker for NSCLC prognosis and suppressed the progression of NSCLC by modulating the activation of PTEN/AKT/PI3K signaling pathway, suggesting that miR-4299 could be a potential target for developing therapies in treating NSCLC.