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MicroRNA deregulation in triple negative breast cancer reveals a role of miR-498 in regulating BRCA1 expression
- Source :
- Repisalud, Instituto de Salud Carlos III (ISCIII), Oncotarget
- Publication Year :
- 2016
- Publisher :
- Impact Journals, 2016.
-
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
- 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
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Repisalud, Instituto de Salud Carlos III (ISCIII), Oncotarget
- Accession number :
- edsair.doi.dedup.....d7e787dfe5ce4b3a13fc1848124666a4