Department of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan.
Preclinical Research Center, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan.
Lab Invest. 2020 Jun;100(6):863-873. doi: 10.1038/s41374-020-0409-4. Epub 2020 Feb 17.
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.
在乳腺癌患者中，原发性化疗常常由于化疗耐药性乳腺癌干细胞（BCSCs）的存活而失败，这导致肿瘤的复发和转移。然而，决定 BCSC 化疗耐药性的因素仍有待研究。在这里，我们对亲本贴壁乳腺癌细胞和 BCSC 模拟的球体衍生癌细胞之间的一系列差异表达 microRNA（miRNA）进行了分析，并确定 hsa-miR-27a 是 BCSC 存活和化疗耐药性的负调节剂。在球体中，我们发现 hsa-miR-27a 的表达下调，hsa-miR-27a 的异位过表达减少了球体的数量和大小。此外，hsa-miR-27a 的过表达通过下调抗氧化物质（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一种潜在治疗方法。
