EBV-encoded miRNAs can sensitize nasopharyngeal carcinoma to chemotherapeutic drugs by targeting BRCA1.
J Cell Mol Med
; 24(22): 13523-13535, 2020 11.
Article
en En
| MEDLINE
| ID: mdl-33074587
ABSTRACT
Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated epithelial malignancy. The high expression of BART-miRNAs (miR-BARTs) during latent EBV infection in NPC strongly supports their pathological importance in cancer progression. Recently, we found that several BART-miRNAs work co-operatively to modulate the DNA damage response (DDR) by reducing Ataxia-telangiectasia-mutated (ATM) activity. In this study, we further investigated the role of miR-BARTs on DDR. The immunohistochemical study showed that the DNA repair gene, BRCA1, is consistently down-regulated in primary NPCs. Using computer prediction programs and a series of reporter assays, we subsequently identified the negative regulatory role of BART2-3p, BART12, BART17-5p and BART19-3p in BRCA1 expression. The ectopic expression of these four miR-BARTs suppressed endogenous BRCA1 expression in EBV-negative epithelial cell lines, whereas BRCA1 expression was enhanced by repressing endogenous miR-BARTs activities in C666-1 cells. More importantly, suppressing BRCA1 expression in nasopharyngeal epithelial cell lines using miR-BART17-5p and miR-BART19-3p mimics reduced the DNA repair capability and increased the cell sensitivity to the DNA-damaging chemotherapeutic drugs, cisplatin and doxorubicin. Our findings suggest that miR-BARTs play a novel role in DDR and may facilitate the development of effective NPC therapies.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
ARN Viral
/
Herpesvirus Humano 4
/
Resistencia a Antineoplásicos
/
Proteína BRCA1
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Infecciones por Virus de Epstein-Barr
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MicroARNs
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Carcinoma Nasofaríngeo
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Año:
2020
Tipo del documento:
Article