通过长非编码RNALIMD1-AS1的SMAD3和p300复合架构促进TGF-β诱导的乳腺癌细胞可塑性
Chuannan Fan1, Davy Cats2, Miriam Selle3
1Oncode Institute and Department of Cell and Chemical Biology, Leiden University Medical Center,Leiden, 2300 RC, the Netherlands.
Nucleic acids research
|September 1, 2025
概括
一个新发现的长非编码RNA,LIMD1-AS1,在乳腺癌中增强了TGF-β信号. 这种分子促进瘤细胞的可塑性和不良预后,
科学领域:
- 分子生物学
- 癌症研究
- 表观遗传学
背景情况:
- 转化生长因子 (TGF) -β信号驱动癌细胞的可塑性通过上皮转化为介质细胞 (EMT).
- 了解TGF-β信号的调节机制对于开发向癌症疗法至关重要.
研究的目的:
- 鉴定和描述乳腺癌中TGF-β信号传递的新型调节剂.
- 研究LIMD1反感RNA1 (LIMD1-AS1) 在TGF-β诱导的EMT和乳腺癌进展中的作用.
主要方法:
- 定量实时PCR用于评估LIMD1-AS1表达.
- 细胞测试以评估EMT,迁移和外流.
- 用于确定分子相互作用的RNA结合测定和共免疫沉.
- 对p300乙转移酶活性进行药理抑制.
主要成果:
- 乳腺癌中的LIMD1- AS1表达上调,与预后不佳相关.
- 减少LIMD1- AS1可以抑制TGF-β诱导的EMT,迁移和扩散.
- 通过促进其与p300的相互作用,LIMD1- AS1增强了SMAD3的转录活性.
- 抑制p300或移位LIMD1-AS1会破坏TGF-β/SMAD信号传递和EMT.
结论:
- 作为TGF-β/ SMAD信号的积极调节者,LIMD1- AS1产生反循环,增强乳腺癌细胞的可塑性.
- 在乳腺癌治疗中,LIMD1- AS1是潜在的治疗点.
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