MiR‑489 promotes apoptosis and inhibits invasiveness of glioma cells by targeting PAK5/RAF1 signaling pathways.

Abstract

Glioma patients receiving therapy are at a high risk of relapse and rapid progression and, thus, more effective treatments are required. The aim of the present study was to determine the suppressive role of miR-489 as an alternative therapeutic target for preventing glioma progression. The results of the present study demonstrated that patients with relatively lower levels of expression of miR-489 had more favorable clinical outcomes. Furthermore, miR-489 expression was inversely correlated with p21-activated kinase 5 (PAK5) mRNA expression levels in glioma specimens. A dual luciferase reporter assay revealed that miR-489 suppressed PAK5 expression by directly targeting the PAK5 3′-untranslated region. The effects of miR-489 on cell viability were measured using MTT and Cell Counting Kit-8 assays. The results demonstrated that ectopic expression of miR-489 mimic decreased cell viability by interfering with cyclin D1 and c-Myc signaling. Additionally, the effect of miR-489 on apoptosis was determined using Hoechst 33258 staining and flow cytometry. The results demonstrated that miR-489 decreased the activity of RAF1, reduced Bcl-2 and promoted Bax expression, resulting in increased cell apoptosis. Furthermore, the effect of miR-489 mimic on cellular motility was assessed using migration and invasion assays. miR-489 was shown to abolish the PAK5/RAF1/MMP2 pathway, resulting in decreased cell invasion ability. These results indicated that miR-489 may be involved in PAK5-mediated regulation of glioma progression, demonstrating the potential therapeutic benefits of targeting miR-489 in glioma.