Project/Area Number |
16H07461
|
Research Category |
Grant-in-Aid for Research Activity Start-up
|
Allocation Type | Single-year Grants |
Research Field |
Drug development chemistry
|
Research Institution | National Cancer Center Japan |
Principal Investigator |
KANEKO SYUZO 国立研究開発法人国立がん研究センター, 研究所, ユニット長 (10777006)
|
Project Period (FY) |
2016-08-26 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
|
Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
Keywords | エピジェネティクス / ヒストン修飾 / NGS解析 / エピゲノム / ヒストンメチル化 / ゲノム解析 / 癌 / バイオマーカー / 分子標的治療薬 |
Outline of Final Research Achievements |
While alterations in epigenetic machinery have been considered to play crucial events in cancer, it has been clear that protein methyltransferases and demethylases are key enzymes at these events. In this study, we analyzed protein expression of lysine demethylase 1 (LSD1) in hepatocellular carcinoma (HCC) samples by immunohistochemistry. To further understand the roles of LSD1 in HCC, we established conditional CRISPR-Cas9 knockout cell lines. We confirmed that HCC patients with high LSD1 expression had significantly lower overall survival rates and higher recurrence rate. In vitro cell proliferation and colony formation assays revealed that depletion of LSD1 resulted in slower cell growth. These results support our results of clinicopathological features and prognostic value in HCC patients. Finally, we developed novel FFPE ChIP-seq technique using antibodies against H3K4me3 and H3K27ac.
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