1. MicroRNA deregulation in triple negative breast cancer reveals a role of miR-498 in regulating BRCA1 expression
- Author
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José Ignacio Arias, Kira Yanowsky, Eduardo Andrés-León, Primitiva Menéndez, Ana Llaneza-Folgueras, Beatriz Martinez-Delgado, María Teresa Vargas, Ricardo González-Cámpora, Nerea Matamala, Rebeca Miñambres, Javier Benitez, Ministerio de Economía y Competitividad (España), [Matamala,N, Yanowsky,K, Benítez,J] Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. [Vargas,MT, González-Cámpora,R] Pathology Service, Hospital Virgen de la Macarena, Sevilla, Spain. [Arias,JI, Menéndez,P]Surgery Service.Pathology Service, Hospital Monte Naranco, Oviedo, Spain.[Andrés-León,E] Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. Bioinformatics Unit, Instituto de Parasitología y Biomedicina 'López Neyra', Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), Granada, Spain. [Llaneza-Folgueras,A] General Surgery Service, Hospital Universitario Central de Asturias, Oviedo, España. [Miñambres,R] Projects Unit, Sistemas Genómicos, Valencia, Spain. [Martínez-Delgado,B] Molecular Genetics Unit, Research Institute of Rare Diseases (IIER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.[Benítez.J] Network on Rare Diseases (CIBERER), Madrid, Spain. [Matamala,N] Molecular Genetics Unit, Research Institute of Rare Diseases (IIER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Vargas,MT] Hematology Service, Hospital Virgen de la Macarena, Sevilla, Spain., and The Spanish Ministry of Economy and Competitiveness (INNPRONTA LIFE project) and FIS PI11/01059 (BM-D).
- Subjects
0301 basic medicine ,Pathology ,Regulación hacia abajo ,Apoptosis ,Triple Negative Breast Neoplasms ,Anatomy::Body Regions::Breast [Medical Subject Headings] ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,0302 clinical medicine ,Anatomy::Cells::Cells, Cultured::Cell Line [Medical Subject Headings] ,Oligonucleótidos ,Neoplasias mamarias animales ,Organisms::Eukaryota::Animals [Medical Subject Headings] ,Medicine ,Luciferasas ,Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Paraffin [Medical Subject Headings] ,skin and connective tissue diseases ,Triple-negative breast cancer ,Cells, Cultured ,Regulation of gene expression ,microRNA ,BRCA1 Protein ,Línea celular ,Mama ,Gene Expression Regulation, Neoplastic ,Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms::Triple Negative Breast Neoplasms [Medical Subject Headings] ,Oncology ,030220 oncology & carcinogenesis ,Female ,DNA microarray ,Research Paper ,medicine.medical_specialty ,Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleotides::Polynucleotides [Medical Subject Headings] ,Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Luciferases [Medical Subject Headings] ,03 medical and health sciences ,Breast cancer ,Downregulation and upregulation ,Biomarkers, Tumor ,Humans ,Cell Proliferation ,Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Down-Regulation [Medical Subject Headings] ,business.industry ,Cell growth ,Parafina ,Diseases::Neoplasms::Neoplasms by Site::Mammary Neoplasms, Animal [Medical Subject Headings] ,Neoplasias de la mama triple negativas ,medicine.disease ,BRCA1 ,Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs [Medical Subject Headings] ,MicroRNAs ,030104 developmental biology ,triple negative breast cancer ,Case-Control Studies ,Cancer research ,business - 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. We thank all members of the Human Cancer Genetics Programme of the Spanish National Cancer Research Centre for all their support. We want to particularly acknowledge the patients, the INCLIVA BioBank (PT13/0010/0004) integrated in the Spanish National Biobanks Network, and Pablo Isidro Marrón, coordinator of Biobanco del Principado de Asturias, for their collaboration. This work has been funded by grants from the Spanish Ministry of Economy and Competitiveness (INNPRONTA LIFE project) and FIS PI11/01059 (BM-D). Sí
- Published
- 2016