在肝细胞癌中,cDCBLD2通过将miR-345-5p与TOP2A编码序列结合而调解索拉芬尼抗性
YeLing Ruan1,2, TianYi Chen1,2, LongBo Zheng3
1Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine - Hangzhou, China.
International journal of biological sciences
|October 2, 2023
概括
循环RNAcDCBLD2通过菌miR-345-5p和稳定TOP2A.通过促进肝细胞癌 (HCC) 中的索拉芬尼抗性. 用siRNA准cDCBLD2在临床前模型中克服了耐药性.
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:
- 索拉芬尼是晚期肝细胞癌 (HCC) 的关键治疗方法.
- 索拉费尼布耐药性显著限制了它在HCC患者的治疗疗效.
- 驱动HCC中索拉芬尼抗性的分子机制在很大程度上是未知的.
研究的目的:
- 调查圆形RNAs在HCC中索拉芬尼抗性的作用.
- 确定克服HCC中索拉芬尼布耐药性的新型治疗点.
主要方法:
- 定量实时PCR测量cDCBLD2和TOP2A的表达.
- 西方涂抹以评估蛋白质水平.
- 路西法酶记者测定以确认miRNA-目标相互作用.
- 细胞活力测试用于评估细胞毒性.
- 使用患者衍生异种移植 (PDX) 模型的动物研究.
主要成果:
- 循环RNAcDCBLD2在抗索拉费尼布的HCC细胞中被上调.
- 抑制cDCBLD2可以增强索拉费尼布诱导的细胞毒性和亡.
- cDCBLD2 作为 miR-345-5p 的分子海绵,增加了 TOP2A mRNA 的稳定性.
- 用siRNA准cDCBLD2可以在HCC PDX模型中逆转索拉芬尼抗性.
结论:
- cDCBLD2是HCC中索拉费尼布耐药性的关键驱动因素.
- cDCBLD2/miR-345-5p/TOP2A轴代表了一个潜在的治疗目标.
- 针对cDCBLD2提供了一个有希望的策略,以克服HCC中索拉芬尼抗性.
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