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通过调节细胞循环,USP9X使CDC123脱和稳定,从而促进乳腺癌发生
Nan Song1, Ling Deng1, Lijie Zeng1
1Department of Hematology, Tianjin Medical University General Hospital, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Molecular carcinogenesis
|June 14, 2023
概括
乳腺癌中细胞分裂周期123 (CDC123) 的高表达与预后不佳相关. 杜比基因酶USP9X调节CDC123,这表明USP9X/CDC123轴是潜在的乳腺癌干预目标.
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:
- 已知细胞分裂周期123 (CDC123) 参与人类疾病,但其在瘤发生和调节中的作用尚不清楚.
- 了解CDC123法规对于识别癌症中的新治疗点至关重要.
研究的目的:
- 为了研究CDC123在乳腺癌中的作用.
- 为了阐明CDC123丰富的调节机制.
- 探索USP9X/CDC123轴作为治疗点的潜力.
主要方法:
- 对乳腺癌细胞中CDC123表达的定量分析.
- 敲击实验来评估CDC123对扩散的影响.
- 共同免疫沉和二氧化定位测试以确定USP9X作为CDC123调节器.
- 细胞周期分析和基因表达造型.
- 使用WP1130.30抑制USP9X活动.
主要成果:
- CDC123在乳腺癌中高度表达,与预后不佳相关,并促进扩散.
- USP9X在K308处对CDC123进行了二氧化,使其表达稳定.
- 在乳腺癌细胞中,USP9X和CDC123的水平是正相关的.
- 删除USP9X或CDC123会导致G0/G1细胞周期停止并抑制增殖.
- 抑制USP9X (WP1130) 阻断G0/G1中的细胞,这种效应是由CDC123过度表达所拯救的.
结论:
- USP9X/CDC123轴通过调节细胞循环促进乳腺癌的发展.
- USP9X是通过duebiquitination通过CDC123丰度的一个关键调节器.
- USP9X/CDC123通路代表了乳腺癌干预的潜在治疗标.
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