In patients with breast cancer, primary chemotherapy often fails due to survival of chemoresistant breast cancer stem cells (BCSCs) which results in recurrence and metastasis of the tumor. However, the factors determining the chemoresistance of BCSCs have remained to be investigated. Here, we profiled a series of differentially expressed microRNAs (miRNAs) between parental adherent breast cancer cells and BCSC-mimicking mammosphere-derived cancer cells, and identified hsa-miR-27a as a negative regulator for survival and chemoresistance of BCSCs. In the mammosphere, we found that the expression of hsa-miR-27a was downregulated, and ectopic overexpression of hsa-miR-27a reduced both number and size of mammospheres. In addition, overexpression of hsa-miR-27a sensitized breast cancer cells to anticancer drugs by downregulation of genes essential for detoxification of reactive oxygen species (ROS) and impairment of autophagy. Therefore, enhancing the hsa-miR-27a signaling pathway can be a potential therapeutic modality for breast cancer.

中文翻译：

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miR-27a 通过破坏活性氧稳态和损害自噬来改善乳腺癌细胞的化学耐药性。

在乳腺癌患者中，由于化疗耐药乳腺癌干细胞 (BCSC) 的存活导致肿瘤复发和转移，初次化疗往往失败。然而，决定 BCSC 化疗耐药性的因素仍有待研究。在这里，我们分析了亲本贴壁乳腺癌细胞和 BCSC 模拟乳腺球衍生癌细胞之间的一系列差异表达的 microRNA (miRNA)，并将 hsa-miR-27a 鉴定为 BCSC 存活和化疗耐药的负调节因子。在乳腺球中，我们发现 hsa-miR-27a 的表达被下调，并且 hsa-miR-27a 的异位过表达减少了乳腺球的数量和大小。此外，hsa-miR-27a 的过表达通过下调活性氧 (ROS) 解毒和自噬受损所必需的基因，使乳腺癌细胞对抗癌药物敏感。因此，增强 hsa-miR-27a 信号通路可能是乳腺癌的潜在治疗方式。