免疫抑制性SOX9-AS1通过调节Wnt信号通路抵抗三阴性乳腺癌衰老
1Department of Breast and Thyroid Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, PR China.
Journal of cellular and molecular medicine
|November 17, 2024
概括
SOX9-AS1,一个长非编码RNA,通过抑制衰老和Wnt信号传递,促进三阴性乳腺癌. 抑制SOX9-AS1可能会增强TNBC中治疗诱导的衰老和免疫反应.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 三重阴性乳腺癌 (TNBC) 提出了治疗挑战,部分原因是对治疗诱导衰老 (TIS) 的耐药性.
- 长非编码RNAs (lncRNAs) 在癌症进展和衰老调节中发挥作用.
- 识别关键的与衰老相关的lncRNAs (SRlncRNAs) 对于开发新的TNBC治疗策略至关重要.
研究的目的:
- 为了识别参与TNBC衰老的SRlncRNAs.
- 研究SOX9-AS1在TNBC细胞生长,衰老和免疫透中的作用.
- 阐明SOX9-AS1影响TNBC的分子机制.
主要方法:
- 对SRlncRNAs的生物信息挖掘.
- 在体外实验中使用MDA-MD-231 TNBC细胞进行实验.
- 细胞增殖,细胞亡,迁移,入侵和衰老的评估.
- 对Wnt信号通路组件 (GSK-3β/β-catenin) 的分析.
- 免疫透分析.
主要成果:
- 确定了7种SRlncRNA,其中SOX9-AS1在TNBC细胞中表达高.
- SOX9-AS1 knockdown 抑制了 TNBC 细胞生长和恶性表型.
- SOX9-AS1敲击促进了他莫西芬诱导的衰老和衰老相关的分泌表型 (SASP) 因子转录.
- SOX9-AS1通过抑制Wnt信号激活来抵抗衰老.
- 低SOX9-AS1表达与特定免疫细胞 (原始B细胞,CD8+ T细胞,γδ T细胞) 的透增加相关.
结论:
- SOX9-AS1通过Wnt信号通路抵抗衰老来促进TNBC.
- 向抑制SOX9-AS1增强SASP和免疫透,为TNBC的TIS策略提供了潜在的辅助.
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