使用微阵列检测预-miRNA-155结合的诱导性活动
Jaeyoung Pai1, Soonsil Hyun2, Ji Young Hyun1
1National Creative Research Center for Biofunctional Molecules, Department of Chemistry, Yonsei University , Seoul 03722, Korea.
Journal of the American Chemical Society
|January 16, 2016
概括
研究人员发现了两种抑制微RNA-155 (miRNA-155) 处理的基因,这是癌症中的关键基因. 这些抑制剂通过阻断Dicer活性和诱导细胞亡来促进癌细胞死亡.
科学领域:
- 分子生物学
- 癌症学
- 生物化学
背景情况:
- 在各种人类癌症中,MicroRNA-155 (miRNA-155) 经常过度表达,通过抑制亡,它起到强大的瘤基因作用.
- 了解miRNA-155的调节机制对于开发向癌症疗法至关重要.
研究的目的:
- 确定可以抑制前微RNA-155 (前miRNA-155) 功能的特定.
- 研究这些抑制剂在促进癌细胞死亡方面的治疗潜力.
主要方法:
- 基微阵列用于选与前miRNA-155结合的基.
- 进行了体外Dicer抑制测定和基于细胞的实验,以评估已识别的的功能作用.
- 用核磁共振 (NMR) 和分子建模研究来阐明结合机制.
主要成果:
- 鉴定出两种可以有效抑制Dicer介导的预miRNA-155转化为成熟miRNA-155的.
- 这些抑制剂增强了miRNA-155基因的表达,并通过依赖酶的途径诱导癌细胞的细胞死亡.
- 结构研究表明,与前miRNA-155的上部突起和顶端茎环区域结合,阻碍了Dicer处理.
结论:
- 发现了针对miRNA-155前处理的新型抑制剂.
- 通过诱导亡,这些具有治疗癌症的潜力.
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