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CBX7 negatively regulates migration and invasion in glioma via Wnt/?-catenin pathway inactivation.

ABSTRACT: CBX7, a member of the Polycomb-group proteins, plays a significant role in normal and cancerous tissues and has been defined as a tumor suppressor in thyroid, breast and pancreatic cancers. However, its function in glioma remains undefined. CBX7 expression is decreased in glioma, especially in higher grade cases, according to data in the CGGA, GSE16001 and TCGA databases. Further experimental evidence has shown that exogenous CBX7 overexpression induced apoptosis and inhibited cell proliferation, colony formation and migration of glioma cells. In this study, we show that the invasive ability of glioma cells was decreased following CBX7 overexpression and CBX7 overexpression was associated with Wnt/?-catenin pathway inhibition, which also decreased downstream expression of ZEB1, a core epithelial-to-mesenchymal transition factor. This reduction in Wnt signaling is controlled by DKK1, a specific Wnt/?-catenin inhibitor. CBX7 enhances DKK1 expression by binding the DKK1 promoter, as shown in Luciferase reporter assays. Our data confirm that CBX7 inhibits EMT and invasion in glioma, which is manifested by influencing the expression of MMP2, MMP9, E-cadherin, N-cadherin and Vimentin in LN229, T98G cells and primary glioma cells (PGC). Furthermore, as a tumor suppressor, CBX7 expression is pivotal to reduce tumor invasion and evaluate prognosis.

SUBMITTER: Bao Z

PROVIDER: S-EPMC5503594 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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CBX7 negatively regulates migration and invasion in glioma via Wnt/β-catenin pathway inactivation.

Bao Zhongyuan Z Xu Xiupeng X Liu Yinlong Y Chao Honglu H Lin Chao C Li Zheng Z You Yongping Y Liu Ning N Ji Jing J

Oncotarget 20170601 24

CBX7, a member of the Polycomb-group proteins, plays a significant role in normal and cancerous tissues and has been defined as a tumor suppressor in thyroid, breast and pancreatic cancers. However, its function in glioma remains undefined. CBX7 expression is decreased in glioma, especially in higher grade cases, according to data in the CGGA, GSE16001 and TCGA databases. Further experimental evidence has shown that exogenous CBX7 overexpression induced apoptosis and inhibited cell proliferation ...[more]

PMID: 28388562

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Project description:Glioma is the most common type of central nervous system tumor. SWItch/sucrose non‑fermentable (SWI/SNF) is a tumor suppressor that serves an important role in epithelial‑mesenchymal transition (EMT). The present study aimed to identify key molecules involved in the EMT process. SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily c member 2 (SMARCC2) is mutated in and its expression is low in multiple types of cancer. SMARCC2 is the core subunit of the chromatin‑remodeling complex, SWI/SNF. Relative mRNA SMARCC2 expression levels in human glioma tissue were analyzed via reverse transcription‑quantitative PCR, whereas the protein expression levels were determined via immunohistochemistry staining. SMARCC2 expression was knocked down in glioma cells using small interfering RNA (si) and overexpressed by infection with adenovirus vectors carrying SMARCC2 cDNA. Wound healing and Transwell assays were performed to assess cell migration and invasion, respectively. Subsequently, immunofluorescence and western blotting were performed to analyze the expression levels of the oncogene c‑Myc, which is associated with SMARCC2. SMARCC2 combines with C‑MYC to downregulate its expression. Consistent with the results of the bioinformatics analysis, which revealed that the upregulated expression levels of SMARCC2 were associated with a more favorable prognosis in patients with glioma, the mRNA and protein expression levels of SMARCC2 were significantly upregulated in low‑grade glioma tissues compared with high‑grade glioma tissues. The results of the wound healing assay demonstrated that cell migration was significantly increased in the siSMARCC2‑1/3 groups compared with the negative control (NC) group. By contrast, the migratory ability of cells was significantly reduced following transduction with adenovirus overexpressing SMARCC2, which upregulated the expression of SMARCC2, compared with the lentiviral vector‑non‑specific control (LVS‑NC) group. The Transwell assay results further showed that SMARCC2 overexpression significantly inhibited the migratory and invasive abilities of U87MG and LN229 cells compared with the LVS‑NC group. Co‑immunoprecipitation assays were subsequently conducted to validate the binding of SMARCC2 and c‑Myc; the results demonstrated that the expression of c‑Myc was downregulated in adenovirus‑transfected cells compared with LVS‑NC‑transfected cells. The results of the western blotting experiments demonstrated that the expression levels of N‑cadherin, vimentin, snail family transcriptional repressor 1 and β‑catenin were notably downregulated, whereas the expression levels of T‑cadherin were markedly upregulated in cell lines stably overexpressing SMARCC2 compared with the LVS‑NC group. In conclusion, the results of the present study suggested that SMARCC2 may inhibit Wnt/β‑catenin signaling by regulating c‑Myc expression in glioma. SMARCC2 regulates the EMT status of the glioblastoma cell line by mediating the expression of the oncogene C‑MYC to inhibit its migration and invasion ability. Thus, SMARCC2 may function as a tumor suppressor or oncogene by regulating associated oncogenes or tumor suppressor genes.

Dataset Information

CBX7 negatively regulates migration and invasion in glioma via Wnt/?-catenin pathway inactivation.

Publications

CBX7 negatively regulates migration and invasion in glioma via Wnt/β-catenin pathway inactivation.

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