Frontiers in Oncology (Sep 2020)
MicroRNA-33b Suppresses Epithelial–Mesenchymal Transition Repressing the MYC–EZH2 Pathway in HER2+ Breast Carcinoma
- Birlipta Pattanayak,
- Iris Garrido-Cano,
- Anna Adam-Artigues,
- Eduardo Tormo,
- Eduardo Tormo,
- Begoña Pineda,
- Begoña Pineda,
- Begoña Pineda,
- Paula Cabello,
- Elisa Alonso,
- Elisa Alonso,
- Begoña Bermejo,
- Begoña Bermejo,
- Begoña Bermejo,
- Cristina Hernando,
- Cristina Hernando,
- María Teresa Martínez,
- María Teresa Martínez,
- Ana Rovira,
- Ana Rovira,
- Joan Albanell,
- Joan Albanell,
- Joan Albanell,
- Federico Rojo,
- Federico Rojo,
- Octavio Burgués,
- Octavio Burgués,
- Juan Miguel Cejalvo,
- Juan Miguel Cejalvo,
- Ana Lluch,
- Ana Lluch,
- Ana Lluch,
- Ana Lluch,
- Pilar Eroles,
- Pilar Eroles,
- Pilar Eroles
Affiliations
- Birlipta Pattanayak
- Biomedical Research Institute, INCLIVA, Valencia, Spain
- Iris Garrido-Cano
- Biomedical Research Institute, INCLIVA, Valencia, Spain
- Anna Adam-Artigues
- Biomedical Research Institute, INCLIVA, Valencia, Spain
- Eduardo Tormo
- Biomedical Research Institute, INCLIVA, Valencia, Spain
- Eduardo Tormo
- Centro de Investigación Biomédica en Red de Oncología, Instituto de Salud Carlos III Madrid, Spain
- Begoña Pineda
- Biomedical Research Institute, INCLIVA, Valencia, Spain
- Begoña Pineda
- Centro de Investigación Biomédica en Red de Oncología, Instituto de Salud Carlos III Madrid, Spain
- Begoña Pineda
- Department of Physiology, University of Valencia, Valencia, Spain
- Paula Cabello
- Biomedical Research Institute, INCLIVA, Valencia, Spain
- Elisa Alonso
- Centro de Investigación Biomédica en Red de Oncología, Instituto de Salud Carlos III Madrid, Spain
- Elisa Alonso
- Department of Pathology, Hospital Clinico de Valencia, Valencia, Spain
- Begoña Bermejo
- Biomedical Research Institute, INCLIVA, Valencia, Spain
- Begoña Bermejo
- Centro de Investigación Biomédica en Red de Oncología, Instituto de Salud Carlos III Madrid, Spain
- Begoña Bermejo
- Department of Oncology, Hospital Clinico de Valencia, Valencia, Spain
- Cristina Hernando
- Biomedical Research Institute, INCLIVA, Valencia, Spain
- Cristina Hernando
- Department of Oncology, Hospital Clinico de Valencia, Valencia, Spain
- María Teresa Martínez
- Biomedical Research Institute, INCLIVA, Valencia, Spain
- María Teresa Martínez
- Department of Oncology, Hospital Clinico de Valencia, Valencia, Spain
- Ana Rovira
- Cancer Research Program, Institut Hospital del Mar d’Investigacions Mèdiques, Barcelona, Spain
- Ana Rovira
- Department of Medical Oncology, Hospital del Mar, Centro de Investigación Biomédica en Red de Cáncer, Barcelona, Spain
- Joan Albanell
- Cancer Research Program, Institut Hospital del Mar d’Investigacions Mèdiques, Barcelona, Spain
- Joan Albanell
- Department of Medical Oncology, Hospital del Mar, Centro de Investigación Biomédica en Red de Cáncer, Barcelona, Spain
- Joan Albanell
- Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
- Federico Rojo
- Centro de Investigación Biomédica en Red de Oncología, Instituto de Salud Carlos III Madrid, Spain
- Federico Rojo
- Department of Pathology, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Madrid, Spain
- Octavio Burgués
- Centro de Investigación Biomédica en Red de Oncología, Instituto de Salud Carlos III Madrid, Spain
- Octavio Burgués
- Department of Pathology, Hospital Clinico de Valencia, Valencia, Spain
- Juan Miguel Cejalvo
- Biomedical Research Institute, INCLIVA, Valencia, Spain
- Juan Miguel Cejalvo
- Department of Oncology, Hospital Clinico de Valencia, Valencia, Spain
- Ana Lluch
- Biomedical Research Institute, INCLIVA, Valencia, Spain
- Ana Lluch
- Centro de Investigación Biomédica en Red de Oncología, Instituto de Salud Carlos III Madrid, Spain
- Ana Lluch
- Department of Physiology, University of Valencia, Valencia, Spain
- Ana Lluch
- Department of Oncology, Hospital Clinico de Valencia, Valencia, Spain
- Pilar Eroles
- Biomedical Research Institute, INCLIVA, Valencia, Spain
- Pilar Eroles
- Centro de Investigación Biomédica en Red de Oncología, Instituto de Salud Carlos III Madrid, Spain
- Pilar Eroles
- 0COST action CA15204, Brussels, Belgium
- DOI
- https://doi.org/10.3389/fonc.2020.01661
- Journal volume & issue
-
Vol. 10
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.
Keywords
