Journal
CANCERS
Volume 12, Issue 5, Pages -Publisher
MDPI
DOI: 10.3390/cancers12051225
Keywords
ELK3; miR-200a; 3' untranslated region (UTR); post-transcriptional modification; cell migration and invasion; extravasation; breast cancer
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Funding
- Ministry of Education, Science, and Technology [NRF-2019R1A2C1003581]
- Basic Science Research Program through the National Research Foundation of South Korea (NRF) - Ministry of Education [2019R1A6A1A03032888]
- National Research Foundation (NRF) of South Korea [NRF-2019R1I1A1A01060649]
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Triple-negative breast cancer (TNBC) refers to breast cancer that does not have receptors for estrogen, progesterone, and HER2 protein. TNBC accounts for 10-20% of all cases of breast cancers and is characterized by its metastatic aggressiveness, poor prognosis, and limited treatment options. Here, we show that the metastatic nature of TNBC is critically regulated by a functional link between miR-200a and the transcription factor ELK3. We found that the expression levels of miR-200a and the ELK3 mRNA were negatively correlated in the luminal and TNBC subtypes of breast cancer cells. In vitro experiments revealed that miR-200a directly targets the 3' untranslated region (UTR) of the ELK3 mRNA to destabilize the transcripts. Furthermore, ectopic expression of miR-200a impaired the migration and invasion of TNBC cells by reducing the expression level of the ELK3 mRNA. In in vivo studies, transfection of MDA-MB 231 cells (a claudin-low TNBC cell type) with exogenous miR-200a reduced their extravasation into the lung during 48 h after tail vein injection, and co-transfection of the cells with an expression plasmid harboring ELK3 that lacked an intact 3'UTR recovered their extravasation ability. Overall, our findings provide evidences that miR-200a and ELK3 is functionally linked to regulate invasive characteristics of breast cancers.
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