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通过WTAP介导的m6A修饰调节的UBE2D3抑制了质母细胞瘤中temozolomide的化学敏感性

Jing Bao¹, Rui Sun¹, Zhenjiang Pan²

¹Department of Neurosurgery, Shidong Hospital, Yangpu District, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, No. 999, Shiguang Road, Yangpu District, Shanghai, 200438, China.

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|July 31, 2024

概括

乌比奎丁结合酶E2D3 (UBE2D3) 通过稳定其表达,促进质母细胞瘤对泰莫索洛米德 (TMZ) 的抵抗. 抑制UBE2D3可以增强TMZ.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
生物化学生物化学

背景情况:

质母细胞瘤 (GBM) 表现出对泰莫索洛米德 (TMZ) 的耐药性.
在GBM化学抵抗中,无素结合酶E2D3 (UBE2D3) 的作用尚未完全理解.
在GBM恶性瘤和TMZ耐药性中WTAP的参与需要进一步阐明.

研究的目的:

调查UBE2D3在GBM中TMZ耐药性的作用.
为了澄清 GBM 中 UBE2D3 和 WTAP 之间的关联.
通过WTAP/IGF2BP1轴阐明UBE2D3表达的调节机制.

主要方法:

在GBM组织中检测UBE2D3表达的免疫组织化学 (IHC).
基因组丰富分析 (GSEA) 用于途径预测.
在体外 (细胞系) 和体内 (异种移植模型) 的研究评估UBE2D3对TMZ耐药性,细胞活力,细胞亡和DNA损伤的影响.
分子测定包括m6A分析,RNA免疫沉和记者基因测定,以调查WTAP/IGF2BP1介导的UBE2D3.3.1调节.

主要成果:

在GBM组织中,UBE2D3的表达升高,与DNA修复通路有关.
减少UBE2D3表达增强TMZ诱导的亡和DNA损伤,抑制GBM细胞活力和瘤生长.
过度表达UBE2D3会导致TMZ耐药性.
WTAP通过IGF2BP1促进UBE2D3m6A的修饰,稳定UBE2D3并增加瘤恶性和TMZ抗性.

结论:

在GBM中,UBE2D3是TMZ抗性的关键驱动因素.
WTAP-IGF2BP1轴通过m6A修改来调节UBE2D3的稳定性.
准UBE2D3或WTAP-IGF2BP1轴可能是克服GBMTMZ耐药性的治疗策略.

关键词:

质母细胞瘤 (glioblastoma) 是一个 N6-甲基氨酸 (m6A) 的修改泰莫佐洛米德 (Temozolomide) 是一种一种乌比奎丁-结合酶E2D3是E2D3的结合酶.威尔姆斯瘤1-关联蛋白质

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