Sun Piyun, Mu Yulong, Zhang Shuyan
Department of Neurology, The Fourth Affiliated Hospital, Harbin Medical University, No. 37 Jiyuan street, Harbin, Heilongjiang, 150001, China.
Tumour Biol. 2014 Dec;35(12):12721-7. doi: 10.1007/s13277-014-2597-2. Epub 2014 Sep 25.
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-κB) 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 μM BAY 11-7028 to inhibit the NF-κB 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-κB activity and MMP-3 expression was also increased. Taken together, these findings suggest that Bmi-1 promotes glioma cell migration and invasion via NF-κB-mediated upregulation of MMP-3.
基质金属蛋白酶3（MMP - 3）与胶质瘤的发病机制及进展有关。然而，MMP - 3是否参与胶质瘤转移的调控及其机制大多尚不清楚。在本研究中，胶质瘤细胞被稳定转染Bmi - 1小干扰RNA（siRNA）以敲低Bmi - 1，或被瞬时转染Bmi - 1互补DNA（cDNA）以上调Bmi - 1水平，并评估它们对侵袭的影响以及对侵袭相关分子的表达分析。敲低Bmi - 1显著降低了T98G细胞中核因子κB（NF -κB）和MMP - 3的表达及活性。当T98G细胞的Bmi - 1水平上调时，用10μM BAY 11 - 7028处理T98G细胞以抑制NF -κB活性。在Bmi - 1过表达细胞中，BAY 11 - 7028严重消除了Bmi - 1上调诱导的侵袭。Bmi - 1过表达增加了T98G细胞的转移潜能；与此同时，NF -κB活性和MMP - 3表达也增加。综上所述，这些发现表明Bmi - 1通过NF -κB介导的MMP - 3上调促进胶质瘤细胞迁移和侵袭。
