Epstein-Barr virus-encoded miRNAs target ATM-mediated response in nasopharyngeal carcinoma
Refereed conference paper presented and published in conference proceedings


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AbstractNasopharyngeal carcinoma (NPC) is a highly invasive epithelial malignancy that is prevalence in southern China and Southeast Asia. It is well-known to be associated with latent Epstein-Barr virus (EBV) infection. By using small RNA sequencing, we previously established a comprehensive miRNA profile in a panel of NPC samples and revealed that the EBV-encoded miRNAs derived from BamHI-A rightward transcripts (miR-BARTs) are abundantly expressed. The important roles of miR-BARTs in cancer development have been reported extensively. In the present study, we identified multiple putative binding sites of miR-BART5-5p, BART7-3p, BART9-3p and BART14-3p on the 3’-UTR of a critical DNA double-strand break (DSB) repair gene, Ataxia-Telangiectasia-Mutant (ATM). Notably, the expression of these 4 miR-BARTs represented more than 10% of all EBV-encoded miRNAs in NPC cells while downregulation of ATM expression was observed in our local primary NPC samples in both qRT-PCR and immunohistochemical (IHC) staining analysis. In addition, the abilities of miR-BARTs to downregulate ATM expression were demonstrated in the transient transfection experiments. By manipulating the miR-BARTs expression in epithelial cell lines, we further revealed that these four viral miRNAs could inhibit both ionizing radiation (IR)-induced ATM kinase activity and BZLF1-induced viral lytic reactivation. In conclusion, our findings suggest that miR-BART5-5p, BART7-3p, BART9-3p and BART14-3p work co-operatively to modulate DNA damage response and to maintain viral latency, contributing to the NPC tumorigenesis. Acknowledgement: Theme-based Research Scheme (T12-401/13-R) and GRF (14104415 and 14138016), Research Grant Council, Hong Kong.
All Author(s) ListRaymond W. M. Lung, Po-Man Hau, Joanna H. M. Tong, Ka-Hei Lam, Anthony W. H. Chan, Kevin Y. L. Yip, George S. W. Tsao, Kwok-Wai Lo, Ka-Fai To
Name of ConferenceAmerican Association for Cancer Research Annual Meeting 2018
Start Date of Conference14/04/2018
End Date of Conference18/04/2018
Place of ConferenceChicago
Country/Region of ConferenceUnited States of America
Proceedings TitleAACR 2018 Proceedings: Abstracts 1-3027
Year2018
Month4
Volume Number59
Pages122 - 123
LanguagesEnglish-United States

Last updated on 2018-06-12 at 15:22