Downregulation of microRNA-27b-3p enhances tamoxifen resistance in breast cancer by increasing NR5A2 and CREB1 expression.
Cell Death Dis
; 7(11): e2454, 2016 11 03.
Article
em En
| MEDLINE
| ID: mdl-27809310
ABSTRACT
Estrogen-dependent breast cancer is often treated with the aromatase inhibitors or estrogen receptor (ER) antagonists. Tamoxifen as a major ER antagonist is usually used to treat those patients with ERα-positive breast cancer. However, a majority of patients with ERα positive fail to respond to tamoxifen due to the presence of intrinsic or acquired resistance to the drug. Altered expression and functions of microRNAs (miRNAs) have been reportedly associated with tamoxifen resistance. In this study, we investigated the role of miR-27b-3p in resistance of breast cancer to tamoxifen. MiR-27b-3p levels were remarkably reduced in the tamoxifen-resistant breast cancer cells compared with their parental cells. In addition, miR-27b-3p was also significantly downregulated in breast tumor tissues relative to adjacent non-tumor tissues. Moreover, the expression levels of miR-27b-3p were lower in the breast cancer tissues from tamoxifen-resistant patients compared with that from untreated-tamoxifen patients. Notably, tamoxifen repressed miR-27b-3p expression, whereas estrogen induced miR-27b-3p expression in breast cancer cells. Besides, we provided experimental evidences that miR-27b-3p enhances the sensitivity of breast cancer cells to tamoxifen in vitro and in vivo models. More importantly, we validated that miR-27b-3p directly targeted and inhibited the expression of nuclear receptor subfamily 5 group A member 2 (NR5A2) and cAMP-response element binding protein 1 (CREB1) and therefore augmented tamoxifen-induced cytotoxicity in breast cancer. Lastly, miR-27b-3p levels were found to be significantly negatively correlated with both NR5A2 and CREB1 levels in breast cancer tissues. Our findings provided further evidence that miR-27b-3p might be considered as a novel and potential target for the diagnosis and treatment of tamoxifen-resistant breast cancer.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tamoxifeno
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Neoplasias da Mama
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Regulação para Baixo
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Regulação Neoplásica da Expressão Gênica
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Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico
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Receptores Citoplasmáticos e Nucleares
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Resistencia a Medicamentos Antineoplásicos
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MicroRNAs
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article