PDF(Pubmed)
Abstract：
Among breast cancer (BC) subtypes, the most aggressive is triple negative BC (TNBC), which is prone to metastasis. We previously found that microRNA (miR)-194-5p is downregulated at the early stages of TNBC brain metastasis development. Additionally, the transcription factor myocyte enhancer factor 2 (MEF2)C, a bioinformatically predicted miR-194-5p target, was increasingly expressed throughout TNBC brain metastasis formation and disease severity. However, the contributions of these two players to malignant cells\' features remain undetermined. This study aimed at disclosing the role of miR-194-5p and MEF2C in TNBC tumorigenesis. The transfection of 4T1 cells with a silencer for MEF2C or with a pre-miRNA for miR-194-5p was employed to study TNBC cells\' phenotypic alterations regarding epithelial and mesenchymal markers, as well as migratory capability alterations. MEF2C-silenced cells presented a decline in both vimentin and cytokeratin expression, whereas the overexpression of miR-194-5p promoted an increase in cytokeratin and a reduction in vimentin, reflecting the acquisition of an epithelial phenotype. Both treatments reduced TNBC cells\' migration. These results suggest that MEF2C may determine TNBC cells\' invasive properties by partially determining the occurrence of epithelial-mesenchymal transition, while the overexpression of miR-194-5p promotes a decline in TNBC cells\' aggressive behavior and reinforces this miRNA\'s role as a tumor suppressor in TNBC.
摘要：
在乳腺癌（BC）亚型中，最具侵略性的是三阴性BC（TNBC），容易转移。我们先前发现microRNA（miR）-194-5p在TNBC脑转移发展的早期阶段下调。此外,转录因子肌细胞增强因子2(MEF2)C,生物信息预测的miR-194-5p靶标，在整个TNBC脑转移形成和疾病严重程度中越来越多地表达。然而,这两个参与者对恶性细胞特征的贡献仍不确定。本研究旨在揭示miR-194-5p和MEF2C在TNBC肿瘤发生中的作用。用MEF2C的沉默子或miR-194-5p的pre-miRNA转染4T1细胞用于研究TNBC细胞关于上皮和间充质标记的表型改变。以及迁移能力的改变。MEF2C沉默的细胞表现出波形蛋白和细胞角蛋白表达的下降，而miR-194-5p的过表达促进了细胞角蛋白的增加和波形蛋白的减少，反映了上皮表型的获得。两种处理都减少了TNBC细胞的迁移。这些结果表明，MEF2C可能通过部分确定上皮-间质转化的发生来确定TNBC细胞的侵袭特性，而miR-194-5p的过表达促进了TNBC细胞攻击行为的下降，并加强了该miRNA在TNBC中作为肿瘤抑制因子的作用。
