miR-593 inhibits proliferation and invasion and promotes apoptosis in non-small cell lung cancer cells by targeting SLUG-associated signaling pathways

Increasing evidence suggests that microRNAs (miRNAs or miRs) serve a critical role in tumor development. However, the role of miRNAs in non-small cell lung cancer (NSCLC) progression remains largely unknown. The present study observed that miR-593 was significantly impaired in patients with NSCLC and was a novel regulator of NSCLC progression. Patients whose tumors had high expression levels of miR-593 had longer overall survival than patients whose tumors had low levels of miR-593 expression (P=0.0219). miR-593 expression levels were inversely correlated with zinc finger protein SNAI2 (SLUG) messenger RNA (mRNA) levels in 87 clinical tissue specimens of NSCLC (P<0.001). A luciferase assay demonstrated that miR-593 interacted with the binding sites present in the SLUG 3′-untranslated region and reduced the expression of SLUG. Introduction of a miR-593 mimic suppressed cell proliferation by inactivating the SLUG/protein kinase B (Akt)/cyclin D1/CDK4 or CDK6 signaling pathway, while it induced apoptosis by activating the SLUG/Akt/Bcl-2/BAX signaling pathway. Furthermore, introduction of a miR-593 mimic recovered the expression of E-cadherin at the protein and mRNA level, and inhibited cell migration and invasion. In conclusion, these results indicated that miR-593 may act as a tumor suppressor in NSCLC to decelerate cancer aggressiveness by inhibiting SLUG expression.