2024-03-29T08:55:04Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/96172023-10-09T11:57:19Zcom_20.500.12105_2174com_20.500.12105_2051com_20.500.12105_2173com_20.500.12105_2102com_20.500.12105_2052col_20.500.12105_2175col_20.500.12105_2103
Repisalud
author
Matamala, Nerea
author
Vargas, Maria Teresa
author
González-Cámpora, Ricardo
author
Arias, Jose Ignacio
author
Menéndez, Primitiva
author
Andrés-León, Eduardo
author
Yanowsky, Kira
author
Llaneza-Folgueras, Ana
author
Miñambres, Rebeca
author
Martinez-Delgado, Beatriz
author
Benitez, Javier
funder
Ministerio de Economía y Competitividad (España)
2020-04-17T16:14:46Z
2020-04-17T16:14:46Z
2016-04-12
Oncotarget. 2016 Apr 12;7(15):20068-79.
1949-2553
http://hdl.handle.net/20.500.12105/9617
26933805
10.18632/oncotarget.7705
1949-2553
Oncotarget
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.
eng
BRCA1
microRNA
triple negative breast cancer
MicroRNA deregulation in triple negative breast cancer reveals a role of miR-498 in regulating BRCA1 expression
journal article
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URL
https://repisalud.isciii.es/bitstream/20.500.12105/9617/1/MicroRNADeregulationInTriple2016.pdf
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MicroRNADeregulationInTriple2016.pdf
URL
https://repisalud.isciii.es/bitstream/20.500.12105/9617/3/MicroRNADeregulationInTriple2016.pdf.txt
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MicroRNADeregulationInTriple2016.pdf.txt