miR-655 suppresses epithelial-to-mesenchymal transition by targeting Prrx1 in triple-negative breast cancer.
miR-655 suppresses epithelial-to-mesenchymal transition by targeting Prrx1 in triple-negative breast cancer.
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miR-655 通过靶向三阴性乳腺癌中的 Prrx1 抑制上皮间质转化。
DOI：
10.1111/jcmm.12770
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发表时间：
2016-05
影响因子：
5.3
通讯作者：
Wang HB
中科院分区：
文献类型：
--
作者：
Lv ZD;Kong B;Liu XP;Jin LY;Dong Q;Li FN;Wang HB
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。上皮间质转化（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过表达可能抑制EMT及其相关的TNBC特征。miR-655的异位表达不仅诱导了细胞角蛋白的上调和波形蛋白表达的降低，而且还抑制了间充质样癌细胞的迁移和侵袭，伴随着向上皮表型的形态学转变。此外，我们发现miR-655在细胞系和临床样本中与Prrx 1呈负相关。通过Prrx 1 3′-非翻译区荧光素酶报告试验证明，miR-655的过表达显著抑制Prrx 1。我们的研究表明，miR-655通过下调Prrx 1抑制TNBC中EMT表型的获得，从而抑制癌症进展期间的细胞迁移和侵袭。
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.