EBV-encoded miRNAs can sensitize nasopharyngeal carcinoma to chemotherapeutic drugs by targeting BRCA1.
Animals
BRCA1 Protein
/ genetics
Cell Cycle
/ genetics
Cell Line, Tumor
Drug Resistance, Neoplasm
/ genetics
Epstein-Barr Virus Infections
/ complications
Gene Expression Regulation, Neoplastic
Genes, Reporter
Herpesvirus 4, Human
/ genetics
Host-Pathogen Interactions
/ genetics
Humans
Immunohistochemistry
Mice
MicroRNAs
Nasopharyngeal Carcinoma
/ drug therapy
Nasopharyngeal Neoplasms
/ drug therapy
RNA Interference
RNA, Viral
miR-BARTs
BRCA1
Epstein-Barr virus
nasopharyngeal carcinoma
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
03
04
2020
revised:
24
09
2020
accepted:
29
09
2020
pubmed:
20
10
2020
medline:
13
5
2021
entrez:
19
10
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33074587
doi: 10.1111/jcmm.16007
pmc: PMC7701581
doi:
Substances chimiques
BRCA1 Protein
0
BRCA1 protein, human
0
MicroRNAs
0
RNA, Viral
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
13523-13535Informations de copyright
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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