TERT と c-Myc の間の相互作用をブロックする:BRAF^V600E/pTERTの二重変異腫瘍に対する新しい治療戦略

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Jing Wei^1,2,3, Jiazhe Liu^1,2, Yan Zhang^1,2

¹Department of Endocrinology and Metabolism, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.

International journal of biological sciences

|August 27, 2025

まとめ

BRAF V600EとTERTのプロモーター変異が同時に発生すると,攻撃的な癌が発症します. 研究者らは TERT-c-Mycとナノ粒子の相互作用を遮断することで腫瘍の成長を抑制し新しい治療戦略を提供することがわかりました

科学分野:

腫瘍学
分子生物学
生物化学

背景:

BRAF V600EとTERTプロモーター (pTERT) の共存変異は,攻撃的な腫瘍と低生存率に関連しています.
これらの二重変異の腫瘍に対する効果的な治療法は限られており,その基礎となる規制メカニズムは十分に理解されていません.

研究の目的:

二重変異腫瘍におけるBRAFとTERTの相互調節メカニズムを解明する.
TERT-c-Mycの相互作用を標的とした新しい治療戦略を開発する.

主な方法:

分子生物学技術を用いてBRAF,TERT,c- Mycの相互作用を調査した.
c- MycがBRAF転写とPP2Ac発現を調節する役割を評価した.
TERT-c-Myc結合を阻害するペプチド結合オーラナノ粒子 (AuNP-p-CPS62およびAuNP-CPS62) を設計および合成した.
腫瘍細胞の増殖を抑制するナノ粒子の有効性を in vitro と in vivo で評価した.

主要な成果:

c-Mycが中心的な役割を果たすBRAFとTERTが相互に規制されていることが示されました.
c- MycはBRAFの転写を促進し,TERTの相互作用によって安定させられる.
c-MycがPP2Acを抑制し,c-Mycの安定化につながり,腫瘍の進行を促進することを示した.
AuNP-p-CPS62とAuNP-CPS62は,BRAF V600E/pTERTの二重変異がん細胞の増殖を効果的に抑制し,生物安全性が良好であることを確認した.

結論:

BRAF,TERT,c-Myc,PP2Aを含む陽性調節ネットワークは,BRAF V600E/pTERTの二重変異腫瘍の進行を促しています.
ペプチド結合ナノ粒子を用いてTERT-c-Mycの相互作用を妨害することは,これらの攻撃的な癌に対する有望な治療法です.

キーワード:

BRAFV600E変異についてペプチド・ゴールドナノ粒子 c-Mycの安定性について pTERT変異

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