| identifier |
PRJDB5402 |
| type |
bioproject |
| sameAs |
|
| organism |
Homo sapiens
|
| title |
Histone lysine methyltransferase G9a is a novel epigenetic target for the treatment of hepatocellular carcinoma |
| description |
Histone H3 lysine 9 dimethylation (H3K9me2) is mainly regulated by the histone lysine methyltransferase G9a and is associated with the repression of transcription.However, both the role of G9a and the significance of H3K9me2 in hepatocellular carcinoma (HCC) cells remain unclear. In this study, we conducted loss-of-function assay of G9a using short-hairpin RNA and pharmacological interference. Knockdown of G9a reduced H3K9me2 levels and impaired both HCC cell growth and sphere formation.However, transforming growth factor beta1-induced epithelial mesenchymal transition (EMT) was not suppressed by G9a knockdown. Pharmacological inhibition of G9a by BIX-01294 resulted in both cell growth inhibition and induction of apoptosis in HCC cells. Intraperitoneal administration of BIX-01294 suppressed the growth of xenograft tumors generated by implantation of HCC cells in non-obese diabetic/severe combined immunodeficient mice.Immunohistochemical analyses revealed high levels of G9a and H3K9me2 in 36 (66.7%) and 35 (64.8%) primary HCC tissues, respectively. G9a expression levels were significantly positively correlated with H3K9me2 levels in tumor tissues. In contrast, in non-tumor tissues, G9a and H3K9me2 were only observed in biliary epithelial cells and periportal hepatocytes. In conclusion, G9a inhibition impairs anchorage-dependent and -independent cell growth, but not EMT in HCC cells. Our data indicate that pharmacological interference of G9a might be a novel epigenetic approach for the treatment of HCC. |
| data type |
Epigenomics
|
Transcriptome or Gene Expression
|
| publication |
|
| properties ▽ |
{...}
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| dbXrefs |
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| distribution |
JSONJSON-LD
|
| Download |
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| status |
public |
| visibility |
unrestricted-access |
| dateCreated |
2016-12-20T07:49:28+09:00 |
| dateModified |
2018-12-20T13:00:48+09:00 |
| datePublished |
2018-12-20T13:00:48+09:00 |