MYC と エピテリアからメゼンキマへの移行 (EMT) は,肺腺がんにおける循環器リズム障害を独立して予測する
bioRxiv : the preprint server for biology
|September 2, 2025
まとめ
肺がんにおける分子昼間時計の乱れは,MYC発現と細胞状態と関連しています. 高いMYCとメゼンキーマ特性は,アデノカルシノーマにおける昼夜リズム障害に独立して影響する.
科学分野:
- 腫瘍学
- クロノバイオロジー
- 分子生物学
背景:
- 肺アデノカルシノーマでは 分子昼夜時計が乱され,マウスモデルでは腫瘍の成長が促進される.
- ヒトの肺がんにおける昼夜時計の障害の決定因子は不明である.
研究 の 目的:
- ヒト肺腺癌におけるMYC発現,上皮-メゼンキーマ移行 (EMT),および日経時計の障害の相関を調査する.
- 肺腫瘍における昼夜活動障害の新たな決定因子を特定する.
主な方法:
- ヒトの肺腫瘍における遺伝子発現に基づいて,昼夜時計の順序と強さを評価するために,時計相関距離 (CCD) を利用した.
- MYC発現,MYC経路活性化,EMT関連遺伝子プログラムを分析した.
- 肺腺癌細胞における実験的に誘発されたEMTは,TGF-βを用いて昼夜振動への影響を観察した.
主要な成果:
- 高いMYC発現またはMYC経路の活性化が,有意な昼夜リズム障害と相関している.
- 肺の正常なレベルを下回る非常に低いMYC発現の腫瘍も,昼夜障害を示した.
- Epithelial-to-mesenchymal transition (EMT) プログラムとTGF-βシグナリングは,MYCが低い腫瘍で強化された.
- メセンキマ腫瘍はより秩序ある (より強い) 昼夜リズムを示した.
- 肺腺がん細胞におけるTGF-β誘導は,昼夜振動の幅を増加させた.
結論:
- MYCの発現と経路の活性化は,肺腺がんにおける昼夜活動障害の独立した決定因子である.
- TGF-βのような要因によって誘発されるメゼンキマ細胞の状態は,肺がんにおける昼夜リズムにも独立して影響する.
- 腫瘍発生経路 (MYC) と細胞状態の可塑性 (EMT) は,肺腺がんにおける分子時計に大きく影響する.
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