癌症研究
细胞周期蛋白E1
细胞周期蛋白依赖激酶
细胞周期蛋白
细胞周期蛋白A2
乳腺癌
细胞周期蛋白D1
周期素
细胞周期蛋白
细胞周期蛋白D
细胞周期蛋白B1
细胞周期
生物
癌症
细胞周期蛋白依赖激酶1
遗传学
作者
Zijie Cai,Q. Shi,Yudong Li,Liang Jin,Shunying Li,Lok Lam Wong,Jingru Wang,Xiaoting Jiang,Mengdi Zhu,Juan Lin,Qi Wang,Yang Wang,Y Liu,Jun Zhang,Chen Gong,Herui Yao,Yihong Yao,Qiang Liu
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2023-10-06
卷期号:9 (40)
被引量:1
标识
DOI:10.1126/sciadv.adi3821
摘要
CDK4/6 inhibitors (CDK4/6i) plus endocrine therapy are now standard first-line therapy for advanced HR + /HER2 − breast cancer, but developing resistance is just a matter of time in these patients. Here, we report that a cyclin E1–interacting lncRNA (EILA) is up-regulated in CDK4/6i-resistant breast cancer cells and contributes to CDK4/6i resistance by stabilizing cyclin E1 protein. EILA overexpression correlates with accelerated cell cycle progression and poor prognosis in breast cancer. Silencing EILA reduces cyclin E1 protein and restores CDK4/6i sensitivity both in vitro and in vivo. Mechanistically, hairpin A of EILA binds to the carboxyl terminus of cyclin E1 protein and hinders its binding to FBXW7, thereby blocking its ubiquitination and degradation. EILA is transcriptionally regulated by CTCF/CDK8/TFII-I complexes and can be inhibited by CDK8 inhibitors. This study unveils the role of EILA in regulating cyclin E1 stability and CDK4/6i resistance, which may serve as a biomarker to predict therapy response and a potential therapeutic target to overcome resistance.
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