A novel NF-κB/MMP-3 signal pathway involves in the aggressivity of glioma promoted by Bmi-1

Matrix metalloproteinase 3 (MMP-3) is implicated in the pathogenesis and progression of glioma. However, whether MMP-3 participates in the regulation of metastasis and its mechanisms in glioma is mostly unknown. In the present study, glioma cells were stably transfected with Bmi-1 small interfering RNA (siRNA) to knockdown off Bmi-1 or were transiently transfected with Bmi-1 complementary DNA (cDNA) to upregulate the Bmi-1 level and to evaluate their effects on invasion and expression analysis for molecules involved in invasion. Knockdown of Bmi-1 dramatically reduced a nuclear factor kappa B (NF-kappa B) and MMP-3 expression and activity in T98G cells. When the T98G cells were upregulated in the Bmi-1 levels, the T98G cells were treated with 10 mu M BAY 11-7028 to inhibit the NF-kappa B activity. The invasion induced by upregulation of Bmi-1 was severely abolished by BAY 11-7028 in Bmi-1 overexpression cells. The T98G cell metastatic potential was increased by overexpression of Bmi-1; completely at the same time, the NF-kappa B activity and MMP-3 expression was also increased. Taken together, these findings suggest that Bmi-1 promotes glioma cell migration and invasion via NF-kappa B-mediated upregulation of MMP-3.