miR-770-5p regulates EMT and invasion in TNBC cells by targeting DNMT3A

Noyan S., Ozketen A. A., Gürdal H., Gür Dedeoğlu B.

CELLULAR SIGNALLING, cilt.83, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 83
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1016/j.cellsig.2021.109996
  • Dergi Adı: CELLULAR SIGNALLING
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: TNBC, miR-770-5p, Motility and invasion, Epithelial-mesenchymal transition (EMT), DNA METHYLTRANSFERASES, BETA-CATENIN, CANCER, METHYLATION, GENE, PROGRESSION
  • Ankara Üniversitesi Adresli: Evet

Özet

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.