MEF2C and miR-194-5p: New Players in Triple Negative Breast Cancer Tumorigenesis

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...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-09, Vol.24 (18), p.14297
Main Authors: Caetano, Sara, Garcia, Ana Rita, Figueira, Inês, Brito, Maria Alexandra
Format: Article
Language:English
Subjects:
Biomarkers
Brain cancer
Breast cancer
Cells
Cytokeratin
Development and progression
Genotype & phenotype
Infection
Keratin
Kinases
Medical prognosis
Metastasis
MicroRNA
MicroRNAs
Morphology
Proteins
Quantitative analysis
Stem cells
Transcription factors
Tumorigenesis
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms241814297