ミトコンドリアRNAの改変が転移における代謝可塑性を形作る

Sylvain Delaunay¹, Gloria Pascual², Bohai Feng^3,4

¹German Cancer Research Center - Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.

Nature

|June 29, 2022

まとめ

癌細胞はミトコンドリアの特定のRNA変異を使って転移を起こしますミトコンドリアのmRNAトランスレーションをターゲットにすることで癌の広がりを抑制する新しい治療戦略が提供されます

科学分野:

分子生物学
癌研究
メタボリック・プラスティシティ

背景:

転移性がんでは,代謝の可塑性が向上しますが,そのメカニズムは完全に理解されていません.
RNAの改変は遺伝子発現を含む細胞プロセスにおいて重要な役割を果たします.

研究の目的:

NOP2/Sun RNAメチルトランスファーゼ3 (NSUN3) に依存するRNA変異が癌転移を誘発する役割を調査する.
ミトコンドリアのmRNA翻訳が癌細胞の侵入と拡散を促すメカニズムを解明する.

主な方法:

ミトコンドリアのtRNAにおける5メチルサイトシン (m5C) と5フォーマルサイトシン (f5C) 変異の分析
m5C欠乏細胞におけるがん細胞の生存能力,糖分解,ミトコンドリア機能,転移の評価
頭頸部がん患者のミトコンドリア主導の遺伝子シグネチャーの特定

主要な成果:

ミトコンドリアのtRNAにおけるNSUN3依存のm5C変異は,酸化性リン酸化と転移に不可欠である.
m5C欠乏の口腔がん細胞は,正常な原発腫瘍の成長にもかかわらず,代謝可塑性の低下と転移の減少を示しています.
CD36に依存する腫瘍細胞は,侵入と拡散のためにミトコンドリアのm5Cを必要とします.
ミトコンドリア主導の遺伝子シグネチャーは頭頸部がんの転移と進行を予測します

結論:

ミトコンドリアRNAの改変,特にm5Cは,がん細胞の代謝可塑性および転移の重要な調節因子である.
ミトコンドリアのmRNA翻訳をターゲットにすることで,癌の転移を抑制する潜在的な治療戦略が提示されます.

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