miR-27a ameliorates chemoresistance of breast cancer cells by disruption of reactive oxygen species homeostasis and impairment of autophagy
miR-27a ameliorates chemoresistance of breast cancer cells by disruption of reactive oxygen species homeostasis and impairment of autophagy
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DOI：
10.1038/s41374-020-0409-4
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发表时间：
2020-02-17
影响因子：
5
通讯作者：
Kuroda, Masahiko
中科院分区：
文献类型：
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作者：
Ueda, Shinobu;Takanashi, Masakatsu;Kuroda, Masahiko
在乳腺癌患者中，由于耐药乳腺癌干细胞（BCSC）的存活，导致肿瘤复发和转移，原发性化疗通常失败。然而，决定BCSCs耐药性的因素仍有待研究。在这里，我们分析了一系列差异表达的microRNA（miRNA）之间的亲本贴壁乳腺癌细胞和BCSC模拟乳腺球衍生的癌细胞，并确定hsa-miR-27 a作为一个负调节BCSC的生存和化疗耐药性。在乳腺球中，我们发现hsa-miR-27 a的表达下调，hsa-miR-27 a的异位过表达减少了乳腺球的数量和大小。此外，hsa-miR-27 a的过表达通过下调活性氧（ROS）解毒和自噬损伤所必需的基因而使乳腺癌细胞对抗癌药物敏感。因此，增强hsa-miR-27 a信号通路可能是一种潜在的乳腺癌治疗模式。作者分析了亲本贴壁乳腺癌细胞和乳腺癌干细胞（BCSC）模拟乳腺球之间差异表达的microRNA，并确定hsa-miR-27 a通过下调ROS解毒和自噬受损所必需的基因，作为BCSC存活和化疗耐药性的负调节因子。hsa-miR-27 a信号通路的增强可能是乳腺癌的潜在治疗方式。
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.The authors profiled differentially expressed microRNAs between parental adherent breast cancer cells and breast cancer stem cell (BCSC) -mimicking mammospheres, and identified hsa-miR-27a as a negative regulator for survival and chemoresistance of BCSCs by downregulating genes essential for detoxification of ROS and impairing of autophagy. Enhancement of the hsa-miR-27a signaling pathway may be a potential therapeutic modality for breast cancer.