一种由circCAPG编码的新型多CAPG-171aa在三阴性乳腺癌中发挥着关键作用
Runjie Song1, Peilan Guo1, Xin Ren1
1State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Molecular cancer
|July 5, 2023
概括
这项研究表明,circCAPG是一种新的蛋白质编码圆形RNA,通过编码CAPG-171aa.促进三阴性乳腺癌 (TNBC) 的生长和转移. CircCAPG显示出作为TNBC的预后生物标志物和治疗点的潜力.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 三重阴性乳腺癌 (TNBC) 由于异质性和缺乏分子标,因此存在治疗挑战.
- 蛋白质编码循环RNA (circRNAs) 越来越多地被认为对癌症发展起作用.
研究的目的:
- 研究蛋白质编码circRNAs在TNBC的病因和致癌过程中的作用.
- 在TNBC进展中识别和描述circCAPG及其编码的多,CAPG-171aa.
主要方法:
- 重新分析TNBC环RNA表达数据 (GEO:GSE113230,GSE101123) 的结果.
- 使用质谱学和双化酶记者测试来识别circCAPG的多代码功能.
- 评估CAPG-171aa在TNBC有机体和小鼠中的功能,包括增殖和转移分析.
- 涉及免疫沉和RIP-qPCR的机制研究,以阐明与STK38,SMURF1和SLU7.7的相互作用.
主要成果:
- 在TNBC样本中,circCAPG表达升高,与整体存活率 (随访10年,AUC=0.8723) 有积极的相关性.
- Knockdown 的 circCAPG 显著抑制了 TNBC 器官的生长.
- CircCAPG被转化为CAPG-171aa,它通过破坏STK38/SMURF1相互作用来促进瘤生长,防止MEKK2降解.
- SLU7通过与侧面的Alu序列结合来调节circCAPG生物发生.
结论:
- 通过CAPG-171aa,CircCAPG增强了TNBC的增殖和转移,从而激活了MEKK2-MEK1/2-ERK1/2通路.
- SLU7调解circCAPG的形成,突出了一个新的调节机制.
- CircCAPG及其编码的多CAPG-171aa代表了TNBC有前途的预后生物标志物和潜在的治疗点.
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