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

DOI
https://doi.org/10.3389/fonc.2020.01661
Journal volume & issue
Vol. 10

Abstract

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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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