MicroRNA-485 inhibits malignant biological behaviour of glioblastoma cells by directly targeting PAK4
International Journal of Oncology
Glioblastoma (GBM) , which is characterised by rapid growth, cellular heterogeneity, angiogenesis, extensive invasion, hypoxia and necrosis, is the most common histological subtype of glioma in adults. MicroRNA (miRNA) dysregulation is a common feature of human cancers, including GBM. Previous studies have suggested that miRNAs are a novel class of regulatory molecules in various human cancers. Therefore, miRNAs may be investigated as a novel candidate and screening tool in the clinical
... he clinical diagnosis, therapy and prognosis of GBM. Recent accumulating evidence has demonstrated that miRNA-485 (miR-485) is involved in the development and progression of several types of human cancers. However, the expression level, exact role and underlying mechanisms of miR-485 in GBM remain unclear. In this study, miR-485 was downregulated in both GBM tissue specimens and cell lines. miR-485 overexpression inhibited GBM cell proliferation, colony formation, migration and invasion; increased apoptosis in vitro; and reduced tumour growth in vivo. In addition, p21-activated kinase 4 (PAK4) was demonstrated to be a direct and functional target of miR-485 in GBM. Furthermore, PAK4 was upregulated in GBM tissues and negatively correlated with miR-485 expression. Moreover, PAK4 knockdown exhibited a similar effect to miR-485 overexpression in GBM cells. Enforced expression of PAK4 rescued miR-485 tumour-suppressor functions in GBM cells. miR-485 inhibited the activation of the AKT and ERK signalling pathways in GBM. These results indicate that miR-485 acts as a tumour suppressor in GBM by, at least partially, directly targeting PAK4 and regulating the AKT and ERK signalling pathways. Thus, miR-485 may be a potential target for the treatment of patients with GBM.