The miR-29 transcriptome in endocrine-sensitive and resistant breast cancer cells

Abstract Aberrant microRNA expression contributes to breast cancer progression and endocrine resistance. We reported that although tamoxifen stimulated miR-29b-1/a transcription in tamoxifen (TAM)-resistant breast cancer cells, ectopic expression of miR-29b-1/a did not drive TAM-resistance in MCF-7...

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Autores principales:	Penn Muluhngwi, Negin Alizadeh-Rad, Stephany L. Vittitow, Ted S. Kalbfleisch, Carolyn M. Klinge
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8b5d06132f984ad69c6ad61231253870
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spelling	oai:doaj.org-article:8b5d06132f984ad69c6ad612312538702021-12-02T16:07:00ZThe miR-29 transcriptome in endocrine-sensitive and resistant breast cancer cells10.1038/s41598-017-05727-w2045-2322https://doaj.org/article/8b5d06132f984ad69c6ad612312538702017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05727-whttps://doaj.org/toc/2045-2322Abstract Aberrant microRNA expression contributes to breast cancer progression and endocrine resistance. We reported that although tamoxifen stimulated miR-29b-1/a transcription in tamoxifen (TAM)-resistant breast cancer cells, ectopic expression of miR-29b-1/a did not drive TAM-resistance in MCF-7 breast cancer cells. However, miR-29b-1/a overexpression significantly repressed TAM-resistant LCC9 cell proliferation, suggesting that miR-29b-1/a is not mediating TAM resistance but acts as a tumor suppressor in TAM-resistant cells. The target genes mediating this tumor suppressor activity were unknown. Here, we identify miR-29b-1 and miR-29a target transcripts in both MCF-7 and LCC9 cells. We find that miR-29b-1 and miR-29a regulate common and unique transcripts in each cell line. The cell-specific and common downregulated genes were characterized using the MetaCore Gene Ontology (GO) enrichment analysis algorithm. LCC9-sepecific miR-29b-1/a-regulated GO processes include oxidative phosphorylation, ATP metabolism, and apoptosis. Extracellular flux analysis of cells transfected with anti- or pre- miR-29a confirmed that miR-29a inhibits mitochondrial bioenergetics in LCC9 cells. qPCR,luciferase reporter assays, and western blot also verified the ATP synthase subunit genes ATP5G1 and ATPIF1 as bone fide miR29b-1/a targets. Our results suggest that miR-29 repression of TAM-resistant breast cancer cell proliferation is mediated in part through repression of genes important in mitochondrial bioenergetics.Penn MuluhngwiNegin Alizadeh-RadStephany L. VittitowTed S. KalbfleischCarolyn M. KlingeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Penn Muluhngwi Negin Alizadeh-Rad Stephany L. Vittitow Ted S. Kalbfleisch Carolyn M. Klinge The miR-29 transcriptome in endocrine-sensitive and resistant breast cancer cells
description	Abstract Aberrant microRNA expression contributes to breast cancer progression and endocrine resistance. We reported that although tamoxifen stimulated miR-29b-1/a transcription in tamoxifen (TAM)-resistant breast cancer cells, ectopic expression of miR-29b-1/a did not drive TAM-resistance in MCF-7 breast cancer cells. However, miR-29b-1/a overexpression significantly repressed TAM-resistant LCC9 cell proliferation, suggesting that miR-29b-1/a is not mediating TAM resistance but acts as a tumor suppressor in TAM-resistant cells. The target genes mediating this tumor suppressor activity were unknown. Here, we identify miR-29b-1 and miR-29a target transcripts in both MCF-7 and LCC9 cells. We find that miR-29b-1 and miR-29a regulate common and unique transcripts in each cell line. The cell-specific and common downregulated genes were characterized using the MetaCore Gene Ontology (GO) enrichment analysis algorithm. LCC9-sepecific miR-29b-1/a-regulated GO processes include oxidative phosphorylation, ATP metabolism, and apoptosis. Extracellular flux analysis of cells transfected with anti- or pre- miR-29a confirmed that miR-29a inhibits mitochondrial bioenergetics in LCC9 cells. qPCR,luciferase reporter assays, and western blot also verified the ATP synthase subunit genes ATP5G1 and ATPIF1 as bone fide miR29b-1/a targets. Our results suggest that miR-29 repression of TAM-resistant breast cancer cell proliferation is mediated in part through repression of genes important in mitochondrial bioenergetics.
format	article
author	Penn Muluhngwi Negin Alizadeh-Rad Stephany L. Vittitow Ted S. Kalbfleisch Carolyn M. Klinge
author_facet	Penn Muluhngwi Negin Alizadeh-Rad Stephany L. Vittitow Ted S. Kalbfleisch Carolyn M. Klinge
author_sort	Penn Muluhngwi
title	The miR-29 transcriptome in endocrine-sensitive and resistant breast cancer cells
title_short	The miR-29 transcriptome in endocrine-sensitive and resistant breast cancer cells
title_full	The miR-29 transcriptome in endocrine-sensitive and resistant breast cancer cells
title_fullStr	The miR-29 transcriptome in endocrine-sensitive and resistant breast cancer cells
title_full_unstemmed	The miR-29 transcriptome in endocrine-sensitive and resistant breast cancer cells
title_sort	mir-29 transcriptome in endocrine-sensitive and resistant breast cancer cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8b5d06132f984ad69c6ad61231253870
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The miR-29 transcriptome in endocrine-sensitive and resistant breast cancer cells

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