トランスクリプション延長因子は,芽細胞腫における in vivo がんの依存性を表している
Tyler E Miller1,2,3,4, Brian B Liau5,6,7, Lisa C Wallace1
1Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
Nature
|July 6, 2017
まとめ
この研究は,イン・ビボスクリーニングを用いて,膠芽細胞腫の新たな治療標的を明らかにした. JMJD6のような転写延長因子をターゲットにすることで,膠原細胞腫の生存率が向上します.
科学分野:
- 腫瘍学
- 分子生物学
- 遺伝学
背景:
- グリオブラストーマは致命的な脳癌で 治療の選択肢は限られています
- 現在の薬の発見はしばしば in vitro モデルに依存しており,これは in vivo 腫瘍の微小環境を反映していない可能性があります.
研究 の 目的:
- グリオブラストーマの標的発見のための in vivo スクリーニングプラットフォームを開発し,利用する.
- インビヴォ・グリオブラストーマの微小環境に特有の新しい治療標的を特定する.
主な方法:
- オーソトピック患者由来異種移植モデルに対するプールRNA干渉 (RNAi) スクリーニング.
- 生存依存性を比較するために,同時に in vitro と in vivo のスクリーンを実施した.
- 機能的な腫瘍の微小環境で高通量ネガティブ選択スクリーニングを使用した.
主要な成果:
- in vivoおよびin vitroスクリーニングでは,重複しないエッセンシャルクロマチンと転写レギュレータのセットが特定されました.
- グリオブラストーマの生存における重要なインビボ依存性として,転写の休止放出と延長因子を発見した.
- JMJD6をインビボでエンハンサー主導の転写適応を媒介する重要な因子として特定した.
- JMJD6または延長因子をターゲットにすることで,臨床前における芽細胞腫の生存期間が延長されました.
結論:
- In vivoのフェノタイプスクリーニングは,in vitroの方法では見逃された新しいがん依存性を発見するのに強力です.
- 転写延長装置は 結晶芽細胞腫の有望な治療戦略です
- JMJD6および関連因子をターゲットにすることで 膠芽細胞腫の治療の新たな道が開けます
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