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DACH1 inhibits glioma invasion and tumor growth via the Wnt/catenin pathway.

ABSTRACT: Background/aim:Glioma is the most common and malignant nervous system tumor and is associated with high-grade malignancy and high recurrence. The mammalian Dachshund1 (DACH1) is a recognized anti-tumor site and has low expression in several malignant tumors, including glioma. We designed and conducted this study to further determine the mechanism of DACH1 in glioma. Patients and methods:The data collected from specimens of patients with glioma from GSE16011 and REMBRANDT databases were analyzed. The effect of DACH1 on proliferation, migration, and invasion of U87 and U251 cell lines was analyzed in vitro. The symbol targets of the Wnt/?-catenin pathway were also evaluated through Western blot. Results:DACH1 deficiency was found in glioma tissues, and the DACH1 level was negatively correlated with the tumor malignancy. DACH1 overexpression inhibited the tumor proliferation, migration, and invasion. High expression of DACH1 also dampened the Wnt/?-catenin pathway, and the activation of the Wnt/?-catenin pathway partly led to the limited proliferation in glioma cells. Conclusion:Downregulation of DACH1 was related to the malignancy and poor prognosis of patients with glioma, and DACH1 overexpression inhibited the tumor proliferation via the Wnt/?-catenin pathway. These findings might assist in the discovery of novel potential diagnostic and therapeutic targets for DACH1, thereby reducing the malignancy and recurrence of glioma.

SUBMITTER: Wang J

PROVIDER: S-EPMC6149903 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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DACH1 inhibits glioma invasion and tumor growth via the Wnt/catenin pathway.

Wang Jing J Zou Yan Y Wu Xuechao X Chen Mu M Zhang Shuai S Lu Xiaojie X Wang Qing Q

OncoTargets and therapy 20180917

<h4>Background/aim</h4>Glioma is the most common and malignant nervous system tumor and is associated with high-grade malignancy and high recurrence. The mammalian Dachshund1 (DACH1) is a recognized anti-tumor site and has low expression in several malignant tumors, including glioma. We designed and conducted this study to further determine the mechanism of DACH1 in glioma.<h4>Patients and methods</h4>The data collected from specimens of patients with glioma from GSE16011 and REMBRANDT databases ...[more]

PMID: 30271168

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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.

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DACH1 inhibits glioma invasion and tumor growth via the Wnt/catenin pathway.

Publications

DACH1 inhibits glioma invasion and tumor growth via the Wnt/catenin pathway.

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