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MicroRNA-33b Suppresses Epithelial–Mesenchymal Transition Repressing the MYC–EZH2 Pathway in HER2+ Breast Carcinoma

Downregulation of miR-33b has been documented in many types of cancers and is being involved in proliferation, migration, and epithelial–mesenchymal transition (EMT). Furthermore, the enhancer of zeste homolog 2-gene (EZH2) is a master regulator of controlling the stem cell differentiation and the c...

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Detalles Bibliográficos
Autores principales: Pattanayak, Birlipta, Garrido-Cano, Iris, Adam-Artigues, Anna, Tormo, Eduardo, Pineda, Begoña, Cabello, Paula, Alonso, Elisa, Bermejo, Begoña, Hernando, Cristina, Martínez, María Teresa, Rovira, Ana, Albanell, Joan, Rojo, Federico, Burgués, Octavio, Cejalvo, Juan Miguel, Lluch, Ana, Eroles, Pilar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511588/
https://www.ncbi.nlm.nih.gov/pubmed/33014831
http://dx.doi.org/10.3389/fonc.2020.01661
Descripción
Sumario:Downregulation of miR-33b has been documented in many types of cancers and is being involved in proliferation, migration, and epithelial–mesenchymal transition (EMT). Furthermore, the enhancer of zeste homolog 2-gene (EZH2) is a master regulator of controlling the stem cell differentiation and the cell proliferation processes. We aim to evaluate the implication of miR-33b in the EMT pathway in HER2+ breast cancer (BC) and to analyze the role of EZH2 in this process as well as the interaction between them. miR-33b is downregulated in HER2+ BC cells vs healthy controls, where EZH2 has an opposite expression in vitro and in patients’ samples. The upregulation of miR-33b suppressed proliferation, induced apoptosis, reduced invasion, migration and regulated EMT by an increase of E-cadherin and a decrease of ß-catenin and vimentin. The silencing of EZH2 mimicked the impact of miR-33b overexpression. Furthermore, the inhibition of miR-33b induces cell proliferation, invasion, migration, EMT, and EZH2 expression in non-tumorigenic cells. Importantly, the Kaplan–Meier analysis showed a significant association between high miR-33b expression and better overall survival. These results suggest miR-33b as a suppressive miRNA that could inhibit tumor metastasis and invasion in HER2+ BC partly by impeding EMT through the repression of the MYC–EZH2 loop.