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: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/46912
Acceso en línea:http://hdl.handle.net/10230/46912
http://dx.doi.org/10.3389/fonc.2020.01661
Access Level:acceso abierto
Palabra clave:EMT
EZH2
HER2+
MYC
Breast cancer
miRNA-33b
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.

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