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, Begona, Cabello, Paula, Alonso, Elisa, Bermejo, Begona, Hernando, Cristina, Martinez, Maria Teresa, Rovira, Ana, Albanell, Joan, Rojo, Federico, Burgues, Octavio, Cejalvo, Juan Miguel, Lluch, Ana, Eroles, Pilar
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p15054
Acceso en línea:https://incliva.portalinvestigacion.com/publicaciones/15054
Access Level:acceso abierto
Palabra clave:miRNA-33b
EMT
MYC
EZH2
HER2+
breast cancer
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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