MicroRNA-33b Suppresses Epithelial-Mesenchymal Transition Repressing the MYC-EZH2 Pathway in HER2+ Breast Carcinoma
| Autor: | Pattanayak B, Garrido-Cano I, Adam-Artigues A, Tormo E, Pineda B, Cabello P, Alonso E, Bermejo B, Hernando C, Martinez M, Rovira A, Albanell J, Rojo F, Burgues O, Cejalvo J, Lluch A, Eroles P |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Frontiers in Oncology r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA instname |
| ISSN: | 2234-943X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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