miR-582-5p is a potential prognostic marker in human non-small cell lung cancer and functions as a tumor suppressor by targeting MAP3K2.

OBJECTIVE: Emerging evidence has shown that microRNAs (miRNAs) play important roles in tumor development and progression. The aim of the present study was to investigate the role of miR-582-5p in non-small cell lung cancer (NSCLC) and to determine the molecular mechanisms underlying its action.

PATIENTS AND METHODS: Using quantitative RT-PCR, we detected miR-582-5p expression in NSCLC cell lines and primary tumor tissues. The association of miR-582-5p expression with clinicopathological factors and prognosis was statistically analyzed. The effect of miR-582-5p on proliferation was evaluated by CCK-8. Cell migration and invasion were assessed by transwell assay. miR-582-5p target genes were confirmed using luciferase activity, RT-PCR and Western blot assays.

RESULTS: We found that miR-582-5p expression was significantly downregulated in NSCLC cell lines and clinical specimens. Low miR-582-5p expression was significantly associated with lymph node metastasis (p = 0.012) and advanced TNM stage (p = 0.004). Kaplan-Meier assay showed that patients with low expression of miR-582-5p had a shorter overall survival than those with high expression of miR-582-5p (p = 0.0033). Functional experiments demonstrated that overexpression of miR-582-5p suppressed the proliferation, migration and invasion of NSCLC cells in vitro. We identified MAP3K2 as a direct target gene of miR-582-5p in NSCLC cells. In addition, ectopic expression of MAP3K2 restored the effects of miR-582-5p on NSCLC cell proliferation, migration and invasion.

CONCLUSIONS: We showed that miR-582-5p inhibits NSCLC metastasis by targeting MAP3K2 expression and could be used as an independent prognostic biomarker for patients with NSCLC.