腫瘍ゲノミクスに基づく in vivo RNAiスクリーンは,肝がんにおける腫瘍抑制剤を特定します
Lars Zender1, Wen Xue, Johannes Zuber
1Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Cell
|November 18, 2008
まとめ
研究者らは,マウスモデルとRNA干渉スクリーンを用いて,がん発症に不可欠なXPO4を含む13の腫瘍抑制遺伝子を特定しました. このアプローチは,がんゲノムを機能的に注釈するのに役立ちます.
科学分野:
- 腫瘍学 腫瘍学
- ゲノミクスゲノミクスとは
- 分子生物学は分子生物学である.
背景:
- 癌は,多数の乗客とドライバーの変異によって,著しい異質性を表しています.
- 新しい腫瘍抑制遺伝子の特定は,がんの発達と治療戦略を理解するために重要です.
研究 の 目的:
- ヒトの癌に関連する腫瘍抑制遺伝子を機能的に識別する.
- 癌の遺伝子発見のためのインビヴォRNA干渉 (RNAi) スクリーンでの実現可能性を確立する.
主な方法:
- ヒト肝細胞癌で削除された遺伝子のマウスオルトログを標的にする短いヘアピンRNA (shRNA) のコンパイルされたプール.
- モザイクマウスモデルでshRNAのプールをテストし,腫瘍発生を促進する能力を評価しました.
- 癌ゲノミクス,RNA干渉,機能的な遺伝子アノテーションのためのモザイクマウスモデルを組み合わせた.
主要な成果:
- 削除特異的なshRNAプールは,マウスにおける肝がん発生を著しく加速した.
- 13の腫瘍抑制遺伝子を特定し,検証し,12の遺伝子は以前は癌と関連がなかった.
- 核輸出タンパク質であるXPO4とその基質EIF5A2を発見し,ヒト腫瘍で増幅され,肝細胞癌を促進する.
結論:
- In vivo RNAiスクリーンは,がんに関連する遺伝子を発見するための実現可能なアプローチです.
- マウスモデルにおけるゲノムデータを機能スクリーンと組み合わせることで,がんゲノムに効果的に注釈が付けられます.
- XPO4のような新しい腫瘍抑制遺伝子は,がん治療の新たな標的となる可能性がある.
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