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Research
EZH2-mediated epigenetic silencing of ZIC4 in hepatocellular carcinoma
Dongxin Tang
The First Affiliated Hospital of Guiyang University of Chinese Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9608-9198
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: The present study aimed to explore the role of ZIC4 in human liver cancer.
Methods: Illumina450 genome-wide methylation data was downloaded from The Cancer Genome Atlas for 50 available liver tumor/surrounding pairs. Wound healing test, colony formation and flow cytometry assay were utilized to analyze cell migration, survival and apoptosis. The effects of EZH2 and ZIC4 on tumor growth were also investigated through in vivo xenograft and orthotopic implantation experiments.
Results: ZIC4 was hypermethylated in liver cancer tissues and cell lines. EZH2 knockdown and DZNep mediated H3K27me3 contributes to ZIC4 expression. The antitumor effect of EZH2 knockdown on hepatocellular carcinoma growth, metastasis and epithelial-mesenchymal transition progression in vitro were rescued by sh-ZIC4. Downregulation of ZIC4 also rescued the antitumor effect of DZNep in vivo.
Conclusions: Epigenetic silencing of ZIC4 by EZH2 mediated H3K27me3 is an important mechanism in human liver cancer and provide a new therapeutic target for the treatment of hepatocellular carcinoma disease.
Keywords
Hepatocellular Carcinoma; DNA methylation; ZIC4; EZH2; Epithelial-mesenchymal transition
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This is a preprint. It has not completed peer review.
Research
EZH2-mediated epigenetic silencing of ZIC4 in hepatocellular carcinoma
Dongxin Tang
The First Affiliated Hospital of Guiyang University of Chinese Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9608-9198
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 23 May, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: The present study aimed to explore the role of ZIC4 in human liver cancer.
Methods: Illumina450 genome-wide methylation data was downloaded from The Cancer Genome Atlas for 50 available liver tumor/surrounding pairs. Wound healing test, colony formation and flow cytometry assay were utilized to analyze cell migration, survival and apoptosis. The effects of EZH2 and ZIC4 on tumor growth were also investigated through in vivo xenograft and orthotopic implantation experiments.
Results: ZIC4 was hypermethylated in liver cancer tissues and cell lines. EZH2 knockdown and DZNep mediated H3K27me3 contributes to ZIC4 expression. The antitumor effect of EZH2 knockdown on hepatocellular carcinoma growth, metastasis and epithelial-mesenchymal transition progression in vitro were rescued by sh-ZIC4. Downregulation of ZIC4 also rescued the antitumor effect of DZNep in vivo.
Conclusions: Epigenetic silencing of ZIC4 by EZH2 mediated H3K27me3 is an important mechanism in human liver cancer and provide a new therapeutic target for the treatment of hepatocellular carcinoma disease.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7