不调节的miRNA表达和雄激素受体损失在种族不同的三阴性乳腺癌
Shristi Bhattarai1,2, Bruna M Sugita3, Emanuelle Nunes-Souza3
1Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, GA 30144, USA.
International journal of molecular sciences
|January 8, 2025
概括
四重阴性乳腺癌 (QNBC) 不成比例地影响非裔美国女性,与较低的雄激素受体 (AR) 表达和较差的生存率有关. 差异表达的miRNAs可能调节AR,导致QNBC中的这些种族差异.
科学领域:
- 在瘤学瘤学.
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
背景情况:
- 三重阴性乳腺癌 (TNBC) 缺乏雄激素受体 (AR) 表达,称为四重阴性乳腺癌 (QNBC),不成比例地影响非洲血统的女性,与较差的整体存活率 (OS) 相对应.
- 微RNAs (miRNAs) 是TNBC中基因表达的关键调节者,影响关键信号通路,包括AR信号,在种族群体和癌症亚型中表达模式不同.
- 了解QNBC差异背后的分子机制对于开发向疗法和改善受影响人群的治疗结果至关重要.
研究的目的:
- 调查微分表达miRNAs在调节四重阴性乳腺癌 (QNBC) 的AR转录中的作用.
- 探索潜在的miRNA介导机制,为非洲裔美国 (AA) 和欧洲裔美国 (EA) 妇女在QNBC患病率和预后中观察到的种族差异作出贡献.
- 识别针对AR基因的特定miRNAs,并且在AA和EA QNBC患者中表达不同.
主要方法:
- 对种族注释的TNBC患者样本 (n = 129) 的分析,以确定AR表达状态并与生存结果相关联.
- 利用癌症基因组图谱 (TCGA) 的RNA-seq数据来比较AA和EA患者之间的AR mRNA水平.
- 使用生物信息学来识别AA和EA QNBC患者之间差异表达的miRNA,并预测AR基因标.
主要成果:
- 与欧洲裔美国人 (EA) 患者 (57.7%) 相比,QNBC在非洲裔美国人 (AA) 患者 (76.6%) 中更为普遍,AR损失与AA患者的生存率差相关.
- 在TCGA数据中,患有TNBC的AA患者的AR mRNA水平低于EA患者,AR低的AA患者的生存状况明显较差.
- 在AA和EAQNBC患者中,有46个miRNA被差异表达,预计有10个特定的miRNA (miR-1185-5p,miR-1305,miR-3161,miR-3690,miR-494-3p,miR-509-3-5p,miR-619-3p,miR-628-3p,miR-873-5p和miR-877-5p) 针对AR.
结论:
- 失去AR表达是与QNBC的非洲裔美国女性预后较差相关的重要因素.
- 特定的差异表达的miRNAs显示了QNBC中AR表达的调节器的潜力,有助于观察到的种族差异.
- 识别这些miRNA-AR调节通路为AA女性对QNBC更高的敏感性提供了关键的见解,并可能指导未来的治疗策略.
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