Real-time Imaging of the Epithelial-mesenchymal Transition Using MicroRNA-200a Sequence-based Molecular Beacon-conjugated Magnetic Nanoparticles
Overview
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The epithelial-mesenchymal transition (EMT) plays important roles in tumor progression to metastasis. Thus, the development of an imaging probe that can monitor transient periods of the EMT process in live cells is required for a better understanding of metastatic process. Inspired by the fact that the mRNA expression levels of zinc finger E-box-binding homeobox 1 (ZEB1) increase when cells adopt mesenchyme characteristics and that microRNA-200a (miR-200a) can bind to ZEB1 mRNA, we conjugated molecular beacon (MB) mimicking mature miR-200a to magnetic nanoparticles (miR-200a-MB-MNPs) and devised an imaging method to observe transitional changes in the cells during EMT. Transforming growth factor-β1 treated epithelial cells and breast cancer cell lines representing both epithelial and mesenchymal phenotypes were used for the validation of miR-200a-MB-MNPs as an EMT imaging probe. The real-time imaging of live cells acquired with the induction of EMT revealed an increase in fluorescence signals by miR-200a-MB-MNPs, cell morphology alterations, and the loss of cell-cell adhesion. Our results suggest that miR-200a-MB-MNPs can be used as an imaging probe for the real-time monitoring of the EMT process in live cells.
Ieda T, Tazawa H, Okabayashi H, Yano S, Shigeyasu K, Kuroda S Sci Rep. 2019; 9(1):16378.
PMID: 31705021 PMC: 6841984. DOI: 10.1038/s41598-019-52816-z.
Chen Z, Peng Y, Xie X, Feng Y, Li T, Li S Theranostics. 2019; 9(20):5784-5796.
PMID: 31534519 PMC: 6735378. DOI: 10.7150/thno.36545.
Brabletz T, Kalluri R, Nieto M, Weinberg R Nat Rev Cancer. 2018; 18(2):128-134.
PMID: 29326430 DOI: 10.1038/nrc.2017.118.
Dual Functional Roles of Molecular Beacon as a MicroRNA Detector and Inhibitor.
Li W, Chan C, Miller A, Lee C J Biol Chem. 2017; 292(9):3568-3580.
PMID: 28100783 PMC: 5339743. DOI: 10.1074/jbc.M116.765776.
In Vivo Visualization and Characterization of Epithelial-Mesenchymal Transition in Breast Tumors.
Zhao Z, Zhu X, Cui K, Mancuso J, Federley R, Fischer K Cancer Res. 2016; 76(8):2094-2104.
PMID: 26893478 PMC: 4873431. DOI: 10.1158/0008-5472.CAN-15-2662.