Wu Zhihao, Li Xiangli, Cai Xuehong, Huang Chenggang, Zheng Min
Department of Breast Surgery, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuanxi Road, Wenzhou, 325000, Zhejiang, China.
Department of General Surgery, The First People Hospital of Yueyang, 39 Dongmaolin Road, Yueyang, 414000, Hunan, China.
Tumour Biol. 2016 Jun;37(6):7939-50. doi: 10.1007/s13277-015-4665-7. Epub 2015 Dec 23.
Epithelial to mesenchymal transition (EMT) is a critical step in the growth and dissemination of malignant diseases, including breast cancer. It is known that microRNAs (miRNAs) play important roles in the regulation of tumor properties in cancers. However, whether miR-497 contributes to EMT in breast cancer cells remains unknown. Our study demonstrated that the expression of miR-497 was significantly decreased in human breast cancer cell lines and breast cancer specimens. In breast cancer cells, EMT was inhibited and promoted by the over-expression as well as depletion of miR-497, respectively. Dual-Luciferase ReporterAassay confirmed that Slug was a direct target of miR-497. The upregulation of miR-497 in breast cancer cells suppressed cell proliferation and induced apoptosis both in vitro and in vivo. Correlation analysis indicated that miR-497 was highly negatively correlated with Slug expression in breast cancer specimens. The knockdown of Slug expression in breast cancer cells significantly suppressed cell proliferation and promoted apoptosis. Our results suggested that the expression of miR-497 is significantly correlated with EMT in breast cancer cells by regulating Slug at the transcriptional as well as translational levels. Therefore, targeting miR-497 may provide a novel strategy for the treatment of breast cancer.
上皮-间质转化（EMT）是包括乳腺癌在内的恶性疾病生长和扩散过程中的关键步骤。已知微小RNA（miRNA）在癌症肿瘤特性的调控中发挥重要作用。然而，miR-497是否参与乳腺癌细胞的EMT过程仍不清楚。我们的研究表明，miR-497在人乳腺癌细胞系和乳腺癌标本中的表达显著降低。在乳腺癌细胞中，miR-497的过表达和缺失分别抑制和促进了EMT。双荧光素酶报告基因检测证实Slug是miR-497的直接靶点。乳腺癌细胞中miR-497的上调在体外和体内均抑制了细胞增殖并诱导了凋亡。相关性分析表明，miR-497与乳腺癌标本中Slug的表达高度负相关。乳腺癌细胞中Slug表达的敲低显著抑制了细胞增殖并促进了凋亡。我们的结果表明，miR-497的表达通过在转录和翻译水平上调节Slug，与乳腺癌细胞中的EMT显著相关。因此，靶向miR-497可能为乳腺癌治疗提供一种新策略。
