Department of Breast Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.
Central Laboratory of Molecular Biology, The Affiliated Hospital of Qingdao University, Qingdao, China.
J Cell Mol Med. 2016 May;20(5):864-73. doi: 10.1111/jcmm.12770. Epub 2016 Jan 28.
Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype that lacks effective targeted therapies. The epithelial-to-mesenchymal transition (EMT) is a key contributor in the metastatic process. In this study, we found that miR-655 was down-regulated in TNBC, and its expression levels were associated with molecular-based classification and lymph node metastasis in breast cancer. These findings led us to hypothesize that miR-655 overexpression may inhibit EMT and its associated traits of TNBC. Ectopic expression of miR-655 not only induced the up-regulation of cytokeratin and decreased vimentin expression but also suppressed migration and invasion of mesenchymal-like cancer cells accompanied by a morphological shift towards the epithelial phenotype. In addition, we found that miR-655 was negatively correlated with Prrx1 in cell lines and clinical samples. Overexpression of miR-655 significantly suppressed Prrx1, as demonstrated by Prrx1 3'-untranslated region luciferase report assay. Our study demonstrated that miR-655 inhibits the acquisition of the EMT phenotype in TNBC by down-regulating Prrx1, thereby inhibiting cell migration and invasion during cancer progression.
三阴性乳腺癌(TNBC)是一种高度侵袭性的乳腺癌亚型,缺乏有效的靶向治疗方法。上皮-间充质转化(EMT)是转移过程中的关键因素。在这项研究中,我们发现 miR-655 在 TNBC 中下调,其表达水平与乳腺癌的分子分类和淋巴结转移相关。这些发现使我们假设 miR-655 的过表达可能抑制 EMT 及其相关特征。miR-655 的异位表达不仅诱导细胞角蛋白上调和波形蛋白表达下调,还抑制间充质样癌细胞的迁移和侵袭,并伴有向上皮表型的形态转变。此外,我们发现 miR-655 在细胞系和临床样本中与 Prrx1 呈负相关。miR-655 的过表达通过 Prrx1 3'-非翻译区荧光素酶报告试验显著抑制 Prrx1。我们的研究表明,miR-655 通过下调 Prrx1 抑制 TNBC 中 EMT 表型的获得,从而抑制癌症进展过程中的细胞迁移和侵袭。