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27/11/2020 - General information

Research involving Hospital del Mar and led by INCLIVA demonstrates the relationship between miR-33b under-expression and poor prognosis in patients with HER2+ breast cancer

MiR-33b acts as a tumour suppressor that inhibits metastasis in this breast cancer subtype

Research involving doctors and researchers from Hospital del Mar and the Hospital del Mar Medical Research Institute, led by the INCLIVA Health Research Institute at Hospital Clínico in Valencia, directed by Dr. Pilar Eroles, Co-coordinator of the Breast Cancer Biology Research Group, has demonstrated, for the first time, that the under-expression of miR-33b is related to a poor prognosis in patients suffering HER2+, one of the most aggressive breast cancers and associated with a low survival rate.

Proposed mechanism of action, suggesting that EZH2 is an indirect target of miR-33b through MYC regulation in HER2 + breast cancer.

One of the main findings of the study is that miR-33b, a single chain RNA with the ability to regulate the expression of other genes, acts as miRNA, suppressing tumours in HER2+ breast cancer. This could inhibit tumour migration and invasiveness, partly by preventing the epithelium-mesenchyme transition (EMT), a process that is critical during tumorigenesis and metastasis. This new information leads the way to the design of new drugs for treating the HER2+ cancer subtype.

The work, the results of which have recently been published in Frontiers in Oncology, in an article entitled 'MicroRNA-33b Suppresses Epithelial-Mesenchymal Transition Repressing the MYC-EZH2 Pathway in HER2+ Breast Carcinoma' shows that miR-33b is less expressed in HER2+ breast tumour samples compared with normal breast tissue.

This is based on evidence indicating that the EMT is responsible for the invasion and migration of cancer cells and is an initial step towards metastasis. Furthermore, low levels of miR-33b in many cancers and its role in proliferation, migration and the EMT should be documented. The aim of the study was to evaluate the involvement of miR-33b in the EMT pathway in HER2+ breast cancer and to analyse the role of the EZH2 gene, a key regulator in the control of stem cell differentiation and cell proliferation, in this process, as well as the interaction between these.

Quantitative PCR expression studies were performed on HER2+ breast cancer cell lines and patient samples, as well as on healthy controls. Experiments were also conducted on increased and decreased miR-33b function and the relevant genes, to assess changes in the invasiveness, migration and cell cycle effects or apoptosis (programmed cell death to control growth and triggered by signals from the cell itself) of breast cancer cells.

The results suggest miR-33b acts as a tumour suppressor, inhibiting metastasis and invasion in HER2+ breast cancer, in part by preventing the transition of the mesenchymal epithelium by repressing the MYC- EZH2 loop (MYC are a family of proto-oncogenes that under normal conditions are involved in regulating gene expression), and establishing a new miR-33b/MYC/EZH2 axis that modulates the growth and progression of breast cells.

Doctors Ana Rovira and Joan Albanell, from the Molecular Cancer Therapy Research Group at the Hospital del Mar Medical Research Institute in Barcelona (IMIM-Hospital del Mar), and Federico Rojo, from the Jiménez Díaz Foundation in Madrid, took part in the research.

The study was funded by Project PI18/01219 and the Biomedical Research Networking Centre in Cancer CIBERONC (CB16/12/00481) of the Health Research Fund, from the Spanish Ministry of Economy and Competitiveness.

Reference article:

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

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