Dataset Information

MicroRNA-206 attenuates glioma cell proliferation, migration, and invasion by blocking the WNT/?-catenin pathway via direct targeting of Frizzled 7 mRNA.

ABSTRACT: Glioma is one of the most prevalent primary malignant brain tumours among adults, and accumulating evidence has shown that dysregulation of microRNAs (miRNAs) is associated with various types of cancers, including glioma. It is necessary to gain a better understanding of the roles and mechanisms of action of miRNAs in WNT-driven glioblastoma multiforme (GBM). Here, we report that miR-206 inhibits the WNT/?-catenin pathway by directly targeting Frizzled 7 (FZD7) mRNA and functions as a tumour suppressor in glioma. The expression of miR-206 in human glioma samples and glioma cells was assessed by reverse-transcription quantitative PCR, fluorescence in situ hybridisation, and histological analysis. Cell Counting Kit-8, colony formation, 5-ethynyl-2'-deoxyuridine incorporation, flow-cytometric, wound healing, Transwell invasion, and three-dimensional migration assays were performed to examine glioma cell proliferation, migration, and invasion in vitro. The effects of miR-206 in vivo were investigated in a xenograft nude-mouse model. MiR-206 expression was significantly lower in glioma specimens than in normal control samples. FZD7 was confirmed as a direct target gene of miR-206. GBM cell proliferation, migration, and invasion were blocked after restoration of miR-206 expression. Moreover, intracranial glioma models revealed an inhibitory effect of miR-206 on intracranial glioma tumour growth. Our results suggest that miR-206 plays a key role in the blockade of the WNT/?-catenin signalling pathway by down-regulating FZD7 and may be a promising therapeutic agent against malignant glioma and other WNT-driven tumours.

SUBMITTER: Zhou F

PROVIDER: S-EPMC6684916 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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MicroRNA-206 attenuates glioma cell proliferation, migration, and invasion by blocking the WNT/β-catenin pathway via direct targeting of Frizzled 7 mRNA.

Zhou Fengqi F Cao Wenping W Xu Ran R Zhang Junxia J Yu Tianfu T Xu Xiupeng X Zhi Tongle T Yin Jianxing J Cao Shengwu S Liu Ning N Wang Yingyi Y Zhao Chunsheng C

American journal of translational research 20190715 7

Glioma is one of the most prevalent primary malignant brain tumours among adults, and accumulating evidence has shown that dysregulation of microRNAs (miRNAs) is associated with various types of cancers, including glioma. It is necessary to gain a better understanding of the roles and mechanisms of action of miRNAs in WNT-driven glioblastoma multiforme (GBM). Here, we report that miR-206 inhibits the WNT/β-catenin pathway by directly targeting Frizzled 7 (<i>FZD7</i>) mRNA and functions as a tum ...[more]

PMID: 31396362

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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

MicroRNA-206 attenuates glioma cell proliferation, migration, and invasion by blocking the WNT/?-catenin pathway via direct targeting of Frizzled 7 mRNA.

Publications

MicroRNA-206 attenuates glioma cell proliferation, migration, and invasion by blocking the WNT/β-catenin pathway via direct targeting of Frizzled 7 mRNA.

Similar Datasets

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