Journal
CELLULAR SIGNALLING
Volume 83, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2021.109996
Keywords
TNBC; miR-770-5p; Motility and invasion; Epithelial-mesenchymal transition (EMT)
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Funding
- Ankara University Scientific Research Projects Coordination Unit [18L0415001]
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MicroRNA miR-770-5p downregulates Vimentin and Snail expression levels by targeting DNMT3A, while increasing or restoring E-cadherin expression, inhibiting EMT phenotypes, motility, and invasion. Overexpression of miR-770-5p resulted in a loss of mesenchymal characteristics and gain of epithelial phenotype, effectively inhibiting invasion potential driven by EMT.
MicroRNAs (miRNAs) are shown to regulate various processes in cancer like motility and invasion that are key features of the metastatic triple negative breast cancer (TNBCs). Epithelial-mesenchymal transition (EMT) is one of the well-defined cellular transitioning processes characterized with reduced E-cadherin expression and increased mesenchymal molecules such as Vimentin or Snail thereby gives the cells mobility and invasive character. Aberrant DNA methylation by DNA methyltransferases (DNMTs) plays an important role in carcinogenesis. It is well known that DNMTs are required for transcriptional silencing of tumor-associated genes. DNMT3A-induced promoter hypermethylation of E-cadherin has also been known to improve cancer metastasis. Our results indicated that miR-770-5p could downregulate Vimentin and Snail expression levels, while increasing or restoring the expression of E-Cadherin hence, leading to inhibition of EMT phenotypes along with motility and invasion. Specifically, we showed that overexpression of miR-770-5p restored the expression of E-Cadherin in MDA-MB-231 cells via directly targeting DNMT3A. We also observed the change in the spindled shapes showing the loss of mesenchymal characteristics and gain of epithelial phenotype in miR-770-5p overexpressing cells. When considered together, our results show that miR-770-5p could effectively inhibit invasion potential driven by EMT.
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