miR-429 inhibits glioma invasion through BMK1 suppression

The purpose of this research was to examine the relationship between big mitogen-activated protein kinase 1 (BMK1) and miRNA miR-429 and to determine the effect of miR-429 on glioma invasiveness. Immunohistochemistry was used to evaluate BMK1 expression in glioma tissues. Real-time PCR was used to measure the expression of miR-429 and other RNAs. Western blot was used to detect the expression of BMK1 and other related proteins. Wound healing, Matrigel invasion, and chemotaxis assays were performed to detect the invasion and migration of glioma cell lines. The actual binding site of miR-429 to the 3' untranslated region of BMK1 was confirmed by luciferase assay and RNA immunoprecipitation. BMK1 expression was associated with the World Health Organization grading of glioma and inversely correlated with patient survival. Suppression of BMK1 inhibited the migration and invasion of glioma cells by interfering with mesenchymal transition. Additionally, hepatocyte growth factor-induced GSK3β phosphorylation was suppressed through BMK1 knockdown. Interestingly, our findings validated a novel role for miR-429 in suppressing the migration and invasion of glioma by directly inhibiting BMK1 expression. We also found that miR-429 expression in glioma cells and tissues was lower than that in normal cells and adjacent non-neoplastic tissues, and miR-429 overexpression inhibited invasive activity of glioma cells both in vitro and in vivo. Furthermore, our data validated that miR-429 downregulation was due to the hypermethylation of its promoter region. Our results indicated that BMK1 modulation by miR-429 has an important function in glioma invasion both in vitro and in vivo.