HER2 and p95HER2 differentially regulate miRNA expression in MCF-7 breast cancer cells and downregulate MYB proteins through miR-221/222 and miR-503

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RECERCAT Home > Sistema de Salut de Catalunya > Vall d'Hebron Institut d'Oncologia – VHIO > Articles científics - VHIO > View document

To access the full text documents, please follow this link: http://hdl.handle.net/11351/5878

dc.contributor	Institut Català de la Salut
dc.contributor	[Gorbatenko A] Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, USA. [Søkilde R, Newie I, Persson H] BioCare, Strategic Cancer Research Program, Lund, Sweden. Department of Clinical Sciences Lund, Oncology and Pathology, Faculty of Medicine, Lund University, Lund, Sweden. [Sorensen EE] Section for Cell Biology and Physiology, Department of Biology, Faculty of Science, University of Copenhagen, Universitetsparken 13, DK-2100, Copenhagen, Denmark. [Morancho B] Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. CIBERONC. [Arribas J] Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. CIBERONC. Departament de Bioquímica i de Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. Institució Catalana de Recerca i Estudis Avançats, JA, Barcelona, Spain
dc.contributor	Hospital Universitari Vall d'Hebron
dc.contributor.author	Gorbatenko, Andrej
dc.contributor.author	Søkilde, Rolf
dc.contributor.author	Sorensen, Ester E.
dc.contributor.author	Newie, Inga
dc.contributor.author	Persson, Helena
dc.contributor.author	Morancho Armisen, Beatriz
dc.contributor.author	Arribas López, Joaquin Vicente
dc.date	2021-04-20T11:30:02Z
dc.date	2021-04-20T11:30:02Z
dc.date	2019-03-04
dc.identifier	Gorbatenko A, Søkilde R, Sorensen EE, Newie I, Persson H, Morancho B, et al. HER2 and p95HER2 differentially regulate miRNA expression in MCF-7 breast cancer cells and downregulate MYB proteins through miR-221/222 and miR-503. Sci Rep. 2019 Mar 4;9(1):3352.
dc.identifier	2045-2322
dc.identifier	http://hdl.handle.net/11351/5878
dc.identifier	10.1038/s41598-019-39733-x
dc.identifier	30833639
dc.identifier	000460123600024
dc.identifier.uri	http://hdl.handle.net/11351/5878
dc.format	application/pdf
dc.language	eng
dc.publisher	Nature Publishing Group
dc.relation	Scientific Reports;9(1)
dc.relation	https://www.nature.com/articles/s41598-019-39733-x
dc.relation	info:eu-repo/grantAgreement/ES/PE2013-2016/PI16%2F00253
dc.rights	Attribution 4.0 International
dc.rights	http://creativecommons.org/licenses/by/4.0/
dc.rights	info:eu-repo/semantics/openAccess
dc.source	Scientia
dc.subject	Mama - Càncer
dc.subject	Cèl·lules canceroses
dc.subject	DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms
dc.subject	ANATOMY::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor::MCF-7 Cells
dc.subject	ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama
dc.subject	ANATOMÍA::células::células cultivadas::línea celular::línea celular tumoral::células MCF-7
dc.title	HER2 and p95HER2 differentially regulate miRNA expression in MCF-7 breast cancer cells and downregulate MYB proteins through miR-221/222 and miR-503
dc.type	info:eu-repo/semantics/article
dc.type	info:eu-repo/semantics/publishedVersion
dc.description.abstract	Mecanismes de la malaltia; Càncer de mama
dc.description.abstract	Mecanismos de la enfermedad; Cáncer de mama
dc.description.abstract	Disease Mechanisms; Breast Cancer
dc.description.abstract	The HER2 oncogene and its truncated form p95HER2 play central roles in breast cancer. Here, we show that although HER2 and p95HER2 generally elicit qualitatively similar changes in miRNA profile in MCF-7 breast cancer cells, a subset of changes are distinct and p95HER2 shifts the miRNA profile towards the basal breast cancer subtype. High-throughput miRNA profiling was carried out 15, 36 and 60 h after HER2 or p95HER2 expression and central hits validated by RT-qPCR. miRNAs strongly regulated by p95HER2 yet not by HER2, included miR-221, miR-222, miR-503, miR-29a, miR-149, miR-196 and miR-361. Estrogen receptor-α (ESR1) expression was essentially ablated by p95HER2 expression, in a manner recapitulated by miR-221/-222 mimics. c-Myb family transcription factors MYB and MYBL1, but not MYBL2, were downregulated by p95HER2 and by miR-503 or miR-221/-222 mimics. MYBL1 3′UTR inhibition by miR-221/222 was lost by deletion of a single putative miR-221/222 binding sites. p95HER2 expression, or knockdown of either MYB protein, elicited upregulation of tissue inhibitor of matrix metalloprotease-2 (TIMP2). miR-221/222 and -503 mimics increased, and TIMP2 knockdown decreased, cell migration and invasion. A similar pathway was operational in T47D- and SKBr-3 cells. This work reveals important differences between HER2- and p95HER2- mediated miRNA changes in breast cancer cells, provides novel mechanistic insight into regulation of MYB family transcription factors by p95HER2, and points to a role for a miR-221/222– MYB family–TIMP2 axis in regulation of motility in breast cancer cells.
dc.description.abstract	This work was supported by the Danish Council for Independent Research (grants no. 12-126942 and 12-127290 to SFP), by the Hartmann foundation (SFP), Fondation Juchum (SFP), Kirsten og Freddy Johansens Fond (SFP), the Breast Cancer Research Foundation (BCRF-17-008) (JA), Instituto de Salud Carlos III (PI16/00253) (JA) and the Harboe foundation (SFP). Katrine Franklin Mark is gratefully acknowledged for excellent technical assistance. We are grateful to Pascal Pineau from Institut Pasteur, France for the MYBL1 3′UTR/psiCHECK2 construct.

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