截断的SCRIB异型通过HNRNP A1介导的外形16跳转促进乳腺癌转移
Bin Zhang1,2,3, Shao-Han Xie1,2,3, Jun-Yi Hu2,3
1Institute of Genomic Medicine, College of Pharmacy, Jinan University, Guangzhou, 510632, China.
Acta pharmacologica Sinica
|July 4, 2023
概括
截断的SCRIB异型 (SCRIB-S) 通过激活ERK通路来促进乳腺癌转移. 异质核核核糖核蛋白A1 (hnRNP A1) 驱动SCRIB-S的产生,并且准这种相互作用可能会抑制转移.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 乳腺癌转移是死亡的主要原因.
- 脚手架蛋白质SCRIB作为瘤抑制剂,其异常表达促进了转移.
- 通过替代拼接生成的SCRIB存在两个异型 (SCRIB-L和SCRIB-S).
研究的目的:
- 为了研究SCRIB异型在乳腺癌转移中的独特功能.
- 阐明管理SCRIB异形生产的监管机制.
- 为了确定乳腺癌转移的潜在治疗点.
主要方法:
- 在转移性与非转移性细胞中对SCRIB异型的比较分析.
- 细胞和分子分析包括CLIP,RIP和MS2-GFP.
- 使用反感 oligodeoxynucleotides (ASO-SCRIB) 的功能研究.
主要成果:
- 与SCRIB-L不同,SCRIB-S在高度转移的细胞中过度表达,并激活ERK通路,促进转移.
- hnRNP A1与SCRIB前mRNA结合,促进16号外基因跳转和SCRIB-S的产生.
- 针对hNRNP A1结合部位的ASO-SCRIB抑制了SCRIB-S的产生,逆转了ERK通路的激活,并减少了乳腺癌的转移.
结论:
- 通过激活ERK通路,SCRIB-S促进乳腺癌转移.
- hnRNP A1介导的SCRIB替代拼接是驱动转移的一个关键机制.
- 针对 hnRNP A1-SCRIB 相互作用,为乳腺癌提供了一个潜在的治疗策略.
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