MicroRNA-33b suppresses epithelial-mesenchymal transition repressing the MYC-EZH2 pathway in HER2+ breast carcinoma

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 Mestres, Joan; Rojo, Federico; Burgués, Octavio; Cejalvo, Juan M.; Lluch, Ana; Eroles, Pilar

MicroRNA-33b suppresses epithelial-mesenchymal transition repressing the MYC-EZH2 pathway in HER2+ breast carcinoma

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dc.contributor.author Pattanayak, Birlipta
dc.contributor.author Garrido Cano, Iris
dc.contributor.author Adam-Artigues, Anna
dc.contributor.author Tormo, Eduardo
dc.contributor.author Pineda, Begoña
dc.contributor.author Cabello, Paula
dc.contributor.author Alonso, Elisa
dc.contributor.author Bermejo, Begoña
dc.contributor.author Hernando, Cristina
dc.contributor.author Martínez, María Teresa
dc.contributor.author Rovira, Ana
dc.contributor.author Albanell Mestres, Joan
dc.contributor.author Rojo, Federico
dc.contributor.author Burgués, Octavio
dc.contributor.author Cejalvo, Juan M.
dc.contributor.author Lluch, Ana
dc.contributor.author Eroles, Pilar
dc.date.accessioned 2021-03-24T06:58:00Z
dc.date.available 2021-03-24T06:58:00Z
dc.date.issued 2020
dc.description.abstract 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.
dc.format.mimetype application/pdf
dc.identifier.citation Pattanayak B, Garrido-Cano I, Adam-Artigues A, Tormo E, Pineda B, Cabello P, Alonso E, Bermejo B, Hernando C, Martínez MT, Rovira A, Albanell J, Rojo F, Burgués O, Cejalvo JM, Lluch A, Eroles P. MicroRNA-33b suppresses epithelial-mesenchymal transition repressing the MYC-EZH2 pathway in HER2+ breast carcinoma. Front Oncol. 2020; 10:1661. DOI: 10.3389/fonc.2020.01661
dc.identifier.doi http://dx.doi.org/10.3389/fonc.2020.01661
dc.identifier.issn 2234-943X
dc.identifier.uri http://hdl.handle.net/10230/46912
dc.language.iso eng
dc.publisher Frontiers
dc.relation.ispartof Front Oncol. 2020; 10:1661
dc.rights © 2020 Pattanayak, Garrido-Cano, Adam-Artigues, Tormo, Pineda, Cabello, Alonso, Bermejo, Hernando, Martínez, Rovira, Albanell, Rojo, Burgués, Cejalvo, Lluch and Eroles. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword EMT
dc.subject.keyword EZH2
dc.subject.keyword HER2+
dc.subject.keyword MYC
dc.subject.keyword Breast cancer
dc.subject.keyword miRNA-33b
dc.title MicroRNA-33b suppresses epithelial-mesenchymal transition repressing the MYC-EZH2 pathway in HER2+ breast carcinoma
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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