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Experimental cell research v.361 no.1, 2017년, pp.85 - 92   SCI SCIE
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Establishment of twist-1 and TGFBR2 as direct targets of microRNA-20a in mesenchymal to epithelial transition of breast cancer cell-line MDA-MB-231

De, Soumasree (Corresponding author. ); Das, Sayantani ( ); Mukherjee, Srimoyee ( ); Das, Sainy ( ); Sengupta (Bandyopadhyay), Sumita ( );
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    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-β 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-β 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. Highlights Metastatic property and miR-20a level is directly correlated in MDA-MB-231 cell-line. Over-expression of miR-20a down-regulates expression of twist1. twist1 upregulates crucial epithelial markers and down-regulates mesenchymal markers. TGF-β and its receptor, TGFBR2 were found to be targets of miR-20a.


  • 주제어

    Mesenchymal to Epithelial Transition (MET) .   Twist-1 .   miR‐20a .   Cell-migration .   Cell-invasion .   Breast cancer.  

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