title: MicroRNA deregulation in triple negative breast cancer reveals a role of miR-498 in regulating BRCA1 expression.
abstract: Emerging evidence suggests that BRCA1 pathway contributes to the behavior of sporadic triple negative breast cancer (TNBC), but little is known about the mechanisms underlying this association. Considering the central role that microRNAs (miRNAs) play in gene expression regulation, the aim of this study was to identify miRNAs specifically deregulated in TNBC and investigate their involvement in BRCA1 regulation. Using locked nucleic acid (LNA)-based microarrays, expression levels of 1919 miRNAs were measured in paraffin-embedded tissues from 122 breast tumors and 11 healthy breast tissue samples. Differential miRNA expression was explored among the main subtypes of breast cancer, and 105 miRNAs were identified as specific for triple negative tumors. In silico prediction revealed that miR-498 and miR-187-5p target BRCA1, and these results were confirmed by luciferase reporter assay. While miR-187-5p was found overexpressed in a luminal B cell line, miR-498 was highly expressed in a triple negative cell line, Hs578T, and its expression was negatively correlated with the levels of BRCA1. We functionally demonstrated that miR-498 inhibits BRCA1 in breast cancer cell lines, and showed that inhibition of miR-498 led to reduced proliferation in the triple negative cell line Hs578T. Our results indicate that miR-498 regulates BRCA1 expression in breast cancer and its overexpression could contribute to the pathogenesis of sporadic TNBC via BRCA1 downregulation.
authors.affiliation: Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.|Current address: Molecular Genetics Unit, Research Institute of Rare Diseases (IIER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
authors.forename: Nerea
authors.initials: N
authors.lastname: Matamala
authors.affiliation: Pathology Service, Hospital Virgen de la Macarena, Sevilla, Spain.|Current address: Hematology Service, Hospital Virgen de la Macarena, Sevilla, Spain.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Vargas
authors.affiliation: Pathology Service, Hospital Virgen de la Macarena, Sevilla, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: González-Cámpora
authors.affiliation: Surgery Service, Hospital Monte Naranco, Oviedo, Spain.
authors.forename: Jose Ignacio
authors.initials: JI
authors.lastname: Arias
authors.affiliation: Pathology Service, Hospital Monte Naranco, Oviedo, Spain.
authors.forename: Primitiva
authors.initials: P
authors.lastname: Menéndez
authors.affiliation: Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.|Current address: Bioinformatics Unit, Instituto de Parasitología y Biomedicina "López Neyra", Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), Granada, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Andrés-León
authors.affiliation: Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Kira
authors.initials: K
authors.lastname: Yanowsky
authors.affiliation: General Surgery Service, Hospital Universitario Central de Asturias, Oviedo, España.
authors.forename: Ana
authors.initials: A
authors.lastname: Llaneza-Folgueras
authors.affiliation: Projects Unit, Sistemas Genómicos, Valencia, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Miñambres
authors.affiliation: Molecular Genetics Unit, Research Institute of Rare Diseases (IIER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Martínez-Delgado
authors.affiliation: Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.|Network on Rare Diseases (CIBERER), Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Benítez
mesh_terms: D017209:Apoptosis; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor; C578093:MIRN498 microRNA, human; D035683:MicroRNAs
keywords: BRCA1; microRNA; triple negative breast cancer