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Exp Cell Res ; 361(1): 85-92, 2017 12 01.
Article in English | MEDLINE | ID: mdl-28987542

ABSTRACT

Messenchymal to epithelial transition (MET) is a significant physiological phenomenon involved in embryogenesis and cancer. This study aims at investigating the mechanism of microRNA-20a (miR-20a) mediated regulation of mesenchymal to epithelial transition and identification of its direct target genes in breast cancer cell-line, MDA-MB-231. Reduced migratory and invasive property, altered cellular morphology along with reduced capability for attachment to basement membrane was acquired by over-expression of miR-20a in invasive MDA-MB-231 cell-line initially expressing low level of this micro-RNA, indicating direct correlation between abundance of miR-20a and metastatic property. The switch from mesenchymal to epithelial cells mediated by miR-20a involved post-transcriptional down-regulation of twist1, which in turn controls downstream epithelial markers like E-cadherin, claudin and mesenchymal markers like N-cadherin, fibronectin, the crucial players of mesenchymal to epithelial transition (MET). Furthermore, another key component, TGF-ß and one of its receptors (TGFBR2) were found to be down-regulated by miR-20a. Additionally, reporter assay established that post-transcriptional down-regulation of TGFBR2 occurred through direct binding of miR-20a to its 3'UTR, thus abrogating the TGF-ß signaling pathway resulting in inhibition of MET. Delineating the underlying molecular mechanism of miR-20a-mediated MET and defining the target genes will help us to introduce a miRNA-mediated effective therapeutic strategy against breast cancer.


Subject(s)
Breast Neoplasms/pathology , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Nuclear Proteins/metabolism , Protein Serine-Threonine Kinases/metabolism , Receptors, Transforming Growth Factor beta/metabolism , Twist-Related Protein 1/metabolism , Antigens, CD , Apoptosis , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cadherins/genetics , Cadherins/metabolism , Cell Adhesion , Cell Movement , Cell Proliferation , Female , Humans , Nuclear Proteins/genetics , Protein Serine-Threonine Kinases/genetics , Receptor, Transforming Growth Factor-beta Type II , Receptors, Transforming Growth Factor beta/genetics , Tumor Cells, Cultured , Twist-Related Protein 1/genetics
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