MicroRNA-33b Suppresses Epithelial-Mesenchymal Transition Repressing the MYC-EZH2 Pathway in HER2+ Breast Carcinoma.

Autores de INCLIVA

• Chaudhuri Birlipta Pattanayak

  Autor

• Iris Garrido Cano

  Autor

• Anna Adam Artigues

  Autor

• Eduardo Tormo Martin

  Autor

• Begoña Pineda Merlo

  Autor

• Paula Cabello Navarro

  Autor

• Elisa Alonso Yuste

  Autor

• 

  Begoña Bermejo De Las Heras

  Autor

• Cristina Hernando Meliá

  Autor

• 

  Maria Teresa Martinez Martinez

  Autor

• Octavio Burgues Gasion

  Autor

• 

  Juan Miguel Cejalvo Andujar

  Autor

• 

  Ana Lluch Hernández

  Autor

• 

  Pilar Eroles Asensio

  Autor

Participantes ajenos a INCLIVA

• Rovira, Ana
• Albanell, Joan
• Rojo, Federico

Grupos y Plataformas de I+D+i

• Grupo de Investigación en Biología en Cáncer de mama

  

  Leading Researcher

  Pilar Eroles Asensio

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.

© 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

Keywords

• miRNA-33b; EMT; MYC; EZH2; HER2+; breast cancer