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miR‐655 suppresses epithelial‐to‐mesenchymal transition by targeting Prrx1 in triple‐negative breast cancer

机译:miR-655通过靶向三阴性乳腺癌中的Prrx1抑制上皮向间充质转化

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摘要

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.
机译: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-间质转化(EMT)是转移过程的关键因素。在这项研究中,我们发现miR-655在TNBC中被下调,其表达水平与乳腺癌中基于分子的分类和淋巴结转移有关。这些发现使我们假设miR-655过表达可能会抑制EMT及其相关的TNBC特性。 miR-655的异位表达不仅诱导细胞角蛋白的上调和波形蛋白表达的降低,而且抑制了间充质样癌细胞的迁移和侵袭,并伴随着形态上移至上皮表型。此外,我们发现在细胞系和临床样品中,miR-655与Prrx1呈负相关。 miR-655的过表达显着抑制了Prrx1,如Prrx1 3'-非翻译区荧光素酶报告检测所证实。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。

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