RT Journal Article
T1 MicroRNA deregulation in triple negative breast cancer reveals a role of miR-498 in regulating BRCA1 expression.
A1 Matamala, Nerea
A1 González-Cámpora, Ricardo
A1 Arias, Jose Ignacio
A1 Menéndez, Primitiva
A1 Andrés-León, Eduardo
A1 Yanowsky, Kira
A1 Llaneza-Folgueras, Ana
A1 Miñambres, Rebeca
A1 Martínez-Delgado, Beatriz
A1 Benítez, Javier
K1 BRCA1
K1 microRNA
K1 triple negative breast cancer
K1 Mama
K1 Línea celular
K1 Regulación hacia abajo
K1 Luciferasas
K1 Oligonucleótidos
K1 Parafina
K1 Neoplasias mamarias animales
K1 Neoplasias de la mama triple negativas
AB 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.
PB Impact Journals
YR 2016
FD 2016-02-25
LK http://hdl.handle.net/10668/2477
UL http://hdl.handle.net/10668/2477
LA en
NO Matamala N, Vargas MT, González-Cámpora R, Arias JI, Menéndez P, Andrés-León E, Yanowsky K, Llaneza-Folgueras A, Miñambres R, Martínez-Delgado B, Benítez J1. MicroRNA deregulation in triple negative breast cancer reveals a role of miR-498 in regulating BRCA1 expression. Oncotarget. 2016; 7(15):20068-79.
NO JOURNAL ARTICLE;
DS RISalud
RD Apr 11, 2025