title: A novel NF-κB/MMP-3 signal pathway involves in the aggressivity of glioma promoted by Bmi-1.
abstract: 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.
authors.affiliation: Department of Neurology, The Fourth Affiliated Hospital, Harbin Medical University, No. 37 Jiyuan street, Harbin, Heilongjiang, 150001, China.
authors.forename: Piyun
authors.initials: P
authors.lastname: Sun
authors.forename: Yulong
authors.initials: Y
authors.lastname: Mu
authors.forename: Shuyan
authors.initials: S
authors.lastname: Zhang
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1 / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction
chemical_list: C069077:BMI1 protein, human; D016328:NF-kappa B; D034741:RNA, Small Interfering; D063150:Polycomb Repressive Complex 1; D019278:Matrix Metalloproteinase 3