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

Abstract

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. 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. 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. 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.