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Review Article

miRNAs作为乳腺癌干细胞中胆固醇的调节剂:一种克服癌症耐药性的方法

卷 23, 期 6, 2022

发表于: 08 October, 2021

页: [656 - 677] 页: 22

弟呕挨: 10.2174/1389450122666211008140811

价格: $65

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摘要

据推测，埋藏在肿瘤块中的少量癌症干细胞（CSC）会驱动癌症生长并赋予癌症耐药性。然而，到目前为止，由于对 CSC 在癌症发展和生长中作用的机制理解有限，它们的根除尚未实现。胆固醇积累和流出过程已被证明在维持细胞完整性及其对药物的敏感性方面发挥着重要作用，因为改变的胆固醇途径有助于癌症耐药性。新出现的证据表明 miRNA 是 CSC 的调节剂，也是癌细胞中胆固醇途径的调节剂，但迄今为止，两者之间的联系尚未完全确定。在这篇综述中，我们整理了关键信号通路并发表了强调 miRNA 和胆固醇参与 CSC 相关耐药性的证据。此外，我们还使用生物信息学分析来识别可能在分子水平上调节 CSC 中胆固醇途径以促进癌症耐药性的 miRNA。我们的研究结果表明，两种 miRNA（hsa-miR-34a-5p 和 hsa-miR-373-3p）与两种已知的乳腺 CSC 标志物（CD44 和 CD24）相互作用并结合，并介导几种胆固醇相关基因（INSIG2， APOL2、CYP51A1、HDLB 和 DHCR7）。此外，对乳腺癌患者基因表达数据的生存分析表明，这些基因的高表达与较差的无病生存率相关。因此，我们建议靶向这两种 miRNA 可能提供一种通过调节 CSC 中的胆固醇途径来改变细胞对药物反应的方法。

关键词: 癌症干细胞，乳腺癌，miRNAs，胆固醇，癌症耐药，造血干细胞。

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