lncRNA遺伝子PVT1のプロモーターは,腫瘍抑制DNA境界要素である
Seung Woo Cho1, Jin Xu1, Ruping Sun2
1Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
Cell
|May 8, 2018
まとめ
PVT1プロモーターは,そのlncRNAとは独立して腫瘍抑制剤として作用する. このプロモーターの変異は,MYCの調節を妨害し,がんの非コード調節要素を強調することによって,がんの成長を促進します.
科学分野:
- 遺伝学
- 分子生物学
- 癌 研究
背景:
- 非コード変異は癌ゲノムに多く見られるが 解釈は困難である.
- PVT1遺伝子は腫瘍性長いノンコーディングRNA (lncRNA) をコードするが,がんに関連したゲノム変異は他の役割を示唆する.
- PVT1とMYCの腫瘍遺伝子は,染色体8q24の近くに位置しています.
研究 の 目的:
- PVT1 lncRNAとは独立したPVT1プロモーターの腫瘍抑制機能を調査する.
- PVT1プロモーターとMYC腫瘍遺伝子の発現の間の規制関係を明らかにする.
- PVT1 プロモーターの突然変異がガン発症に及ぼす影響を特定する.
主な方法:
- CRISPR干渉 (CRISPRi) によってPVT1プロモーターの活性が抑制される.
- 共有強化剤のプロモーター競争の分析
- 癌ゲノム配列決定とゲノム編集の検証
主要な成果:
- PVT1プロモーターの干渉は乳がん細胞の競争とインビボの増殖を強めた.
- PVT1のプロモーターはMYCのプロモーターとPVT1の内遺伝増強剤との関わりを競う.
- この競争により,PVT1のプロモーターは,MYCのトランスクリプションをパウズリリースで制御することができます.
- PVT1プロモーター変異は癌ゲノムで特定され,癌細胞の成長を促進することが示されました.
結論:
- PVT1プロモーターは,PVT1 lncRNAとは独立した腫瘍抑制機能を有する.
- PVT1とMYCの間のプロモーターの競争は重要な規制メカニズムです.
- PVT1プロモーターの変異は癌の発生に寄与する.
- lncRNA遺伝子の調節配列は,疾患に関連する潜在的なDNA要素を表しています.
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