The Impact of HER2 Overexpression on the miRNA and circRNA Transcriptomes in Two Breast Cell Lines and Their Vesicles

Abstract

HER2 upregulation is related with poor outcome in many tumor types. Whereas anti-HER2 treatment is the standard approach as adjuvant therapy in HER2-overexpressing breast cancer, the frequent relapses reinforce the need for alternative treatments. Here we used next-generation sequencing (NGS) to evaluate miRNAs and circRNAs in the cell-lines HB4a and C5.2, where the latter is a HER2-overexpressing clone of the former, and also from two different populations of their secreted extracellular vesicles. Whereas circRNA-levels were stable, we found at least 16 miRNAs apparently modulated by HER2-expression. The miR223-3p, miR-421 and miR-21-5p were validated in an independent cohort of 431 breast cancer patients from The Cancer Genome Atlas (TCGA). The consistent modulation of these molecules and their possible involvement in the HER2-axis makes them promising new targets to overcome HER2-activation.

Supplementary data

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Financial & competing interests disclosure

This project was financed by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), grants 2011/04399-0; 11/09172-3; 14/26897-0; 17/20278-4). ED-N is a research fellow from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), from Brazil, and also acknowledges the support given by Associação Beneficente Alzira Denise Hertzog Silva (ABADHS). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This project was financed by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), grants 2011/04399-0; 11/09172-3; 14/26897-0; 17/20278-4). ED-N is a research fellow from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), from Brazil, and also acknowledges the support given by Associação Beneficente Alzira Denise Hertzog Silva (ABADHS). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.