Dataset Information

A central role for MeCP2 in the epigenetic repression of miR-200c during epithelial-to-mesenchymal transition of glioma.

ABSTRACT:

Background

The epithelial-to-mesenchymal transition (EMT) has been linked to the regulation of glioma progression. However, the underlying signaling mechanisms that regulate EMT are poorly understood.

Methods

Quantitative real-time PCR (RT-qPCR) and western blot were performed to detect the expression of MeCP2 in glioma tissues and cell lines. MeCP2 functions were tested with cell immunofluorescence staining and western blot. For in vivo experiments, mouse xenograft model was used to investigate the effects of MeCP2 on glioma. ChIP and Co-IP were used to detect the relationships among MeCP2, miR-200c and Suv39H1.

Results

In this study, we found that MeCP2 was frequently up-regulated in human glioma tissues and cell lines. MeCP2 knockdown remarkably induced cell epithelial phenotype and inhibited mesenchymal marker ZEB1 and ZEB2 in vitro and in vivo. In addition, MeCP2 in glioma tissues was negatively correlated with miR-200c expression, and miR-200c overexpression partially abrogated mesenchymal phenotype induced by MeCP2. More importantly, we showed that MeCP2 recruited H3K9 to the promoter of miR-200c by interacting with SUV39H1, resulting in EMT of glioma cells.

Conclusions

This study for the first time reveals MeCP2 as a novel regulator of EMT in glioma and suggest that MeCP2 inhibition may represent a promising therapeutic option for suppressing EMT in glioma.

SUBMITTER: Bian E

PROVIDER: S-EPMC6702741 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

A central role for MeCP2 in the epigenetic repression of miR-200c during epithelial-to-mesenchymal transition of glioma.

Bian Erbao E Chen Xueran X Xu Yadi Y Ji Xinghu X Cheng Meng M Wang Hongliang H Fang Zhiyou Z Zhao Bing B

Journal of experimental & clinical cancer research : CR 20190820 1

<h4>Background</h4>The epithelial-to-mesenchymal transition (EMT) has been linked to the regulation of glioma progression. However, the underlying signaling mechanisms that regulate EMT are poorly understood.<h4>Methods</h4>Quantitative real-time PCR (RT-qPCR) and western blot were performed to detect the expression of MeCP2 in glioma tissues and cell lines. MeCP2 functions were tested with cell immunofluorescence staining and western blot. For in vivo experiments, mouse xenograft model was used ...[more]

PMID: 31429770

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Project description:UnlabelledIntrahepatic cholangiocellular carcinoma (ICC) is the second most common type of primary liver cancer. However, its tumor heterogeneity and molecular characteristics are largely unknown. In this study, we conducted transcriptomic profiling of 23 ICC and combined hepatocellular cholangiocarcinoma tumor specimens from Asian patients using Affymetrix messenger RNA (mRNA) and NanoString microRNA microarrays to search for unique gene signatures linked to tumor subtypes and patient prognosis. We validated the signatures in an additional 68 ICC cases derived from Caucasian patients. We found that both mRNA and microRNA expression profiles could independently classify Asian ICC cases into two main subgroups, one of which shared gene expression signatures with previously identified hepatocellular carcinoma (HCC) with stem cell gene expression traits. ICC-specific gene signatures could predict survival in Asian HCC cases and independently in Caucasian ICC cases. Integrative analyses of the ICC-specific mRNA and microRNA expression profiles revealed that a common signaling pathway linking miR-200c signaling to epithelial-mesenchymal transition (EMT) was preferentially activated in ICC with stem cell gene expression traits. Inactivation of miR-200c resulted in an induction of EMT, whereas activation of miR-200c led to a reduction of EMT including a reduced cell migration and invasion in ICC cells. We also found that miR-200c and neural cell adhesion molecule 1 (NCAM1) expression were negatively correlated and their expression levels were predictive of survival in ICC samples. NCAM1, a known hepatic stem/progenitor cell marker, was experimentally demonstrated to be a direct target of miR-200c.ConclusionOur results indicate that ICC and HCC share common stem-like molecular characteristics and poor prognosis. We suggest that the specific components of EMT may be exploited as critical biomarkers and clinically relevant therapeutic targets for an aggressive form of stem cell-like ICC.

Dataset Information

A central role for MeCP2 in the epigenetic repression of miR-200c during epithelial-to-mesenchymal transition of glioma.

Background

Methods

Results

Conclusions

Publications

A central role for MeCP2 in the epigenetic repression of miR-200c during epithelial-to-mesenchymal transition of glioma.

Similar Datasets

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