Open AccessEBV–encoded miRNAs can sensitize nasopharyngeal carcinoma to chemotherapeutic drugs by targeting BRCA1
Author(s) -
Lung Raymond WaiMing,
Tong Joanna HungMan,
Ip LokMan,
Lam KaHei,
Chan Anthony WingHung,
Chak WingPo,
Chung LauYing,
Yeung Walter Wai,
Hau PokMan,
Chau ShukLing,
Tsao SaiWah,
Lau KinMang,
Lo KwokWai,
To KaFai
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16007
Subject(s) - nasopharyngeal carcinoma , microrna , cancer research , chemotherapeutic drugs , carcinoma , medicine , biology , bioinformatics , cancer , gene , genetics , radiation therapy
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.