Expression Of BRG1in Human Glioma And Regulate Glioma Cell Proliferation, Migration And Invasion In Vitro

Background: Glial tumors are the most common type of primary brain neoplasm andconstitute more than70%of all primary brain tumors. The most malignant histologicaltype is the glioblastoma, less than3%of glioblastoma patients are still alive at5years afterdiagnosis. Current treatment modalities for glioma patients including surgical resection,radiation therapy and chemotherapy, but most of glioblastoma patients survival time is stillapproximately1year. Abnormal activation o oncogene and inactivation of anti-oncogenerelate to the tumor formation of glioma. The exact mechanism of glioma is still unclear,and the lackage of accurate and effective method for early diagnosis is the main cause toinduce the high mortality. Therefore, exploration of genetic alterations closely linked withglioma formation and dissemination would be of great values in prevention, early detection,prognostic evaluation and prolongation live time of this malignancy.The SWI/SNF chromatin remodeling complex plays important roles in cellularprocesses including cell differention, cell cycle control and DNA repair. The studies foundthat aberrant expression of SWI/SNF subunits is involved in cancer development. The coresubunit of the SWI/SNF complex, SNF5, has been shown to be inactivated in malignantrhabdoid tumours and has been defined as a tumour suppressor. However, the role of thecatalytic subunit of the SWI/SNF, BRG1, is not well defined in cancer.Objectives: To investigate the role of BRG1in glioma development, we examined theexpression of BRG1in glioma at different stage and analysed the correlation betweenBRG1expression and clinicopathological variables, and further analysed the effect ofBRG1in glioma cell growth, migration and invasion.Methods: Using tissue microarray and immunohistochemistry, we evaluated BRG1staining in190glioma tissues,8normal brain tissues and8tumor adjacent normal braintissues. We studied glioma cell proliferative ability with reduced BRG1expression bysmall interfering RNA using CCK-8cell proliferation assay and cell cycle analysis. Then，we studied the role of BRG1in glioma cell migration and invasion by Transwell migration assay and matrigel invasion assay. We performed western blot to detect Cyclin D1, CyclinB1and MMP-2protein expression. At the same time,we also detected MMP-2enzymeactivity by gelatin zymography.Results: Our results showed that BRG1expression was increased in benign tumor andmalignant tumor compared with tumor adjacent normal brain tissue (P <0.01). However,there is no significant difference in BRG1staining between benign tumor and malignanttumor (P=0.847, χ2test). We did not find any correlation between BRG1expression andclinicopathological parameters. In addition, we found that knockdown of BRG1in U251and U87glioma cell lines inhibits cell growth due to G1phase arrest by downregulatingCyclin D1and Cyclin B1in vitro assay. We further demonstrated that silence of BRG1inglioma cells inhibited cell migration and invasion abilities, and down-regulation of MMP-2expression greatly contributed to the reduced cell invasion and migration abilities.Conclusions: Our data indicated that BRG1expression is significantly increased inhuman glioma and it may be involved in the process of glioma cell proliferation, migrationand invasion. Knockdown of BRG1may serve a potential therapeutic target for humanglioma.