期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 24, 期 18, 页码 -出版社
MDPI
DOI: 10.3390/ijms241814297
关键词
cytokeratin; epithelial-mesenchymal transition; invasiveness; MEF2C; migration; miR-194-5p; triple negative breast cancer; tumor suppression; tumorigenesis; vimentin
This study reveals the involvement of miR-194-5p and MEF2C in TNBC tumorigenesis. It is found that downregulation of miR-194-5p and upregulation of MEF2C are associated with TNBC brain metastasis development. Silencing MEF2C reduces TNBC cells' epithelial-mesenchymal transition and migration capability, while overexpressing miR-194-5p promotes an epithelial phenotype and decreases the aggressiveness of TNBC cells.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据