Epstein-Barr virus encoded microRNA BART7 regulates radiation sensitivity of nasopharyngeal carcinoma
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Wei Gao1,2, Zeng-Hong Li3, Siqi Chen1,2, Jimmy Yu-Wai Chan1,2, Min Yin4, Min-Juan Zhang1,2, Thian-Sze Wong1,2
1Department of Surgery, The University of Hong Kong, Hong Kong SAR
2Shenzhen Institute of Research and Innovation, The University of Hong Kong, Guangdong Province, China
3Department of Otolaryngology, The First People's Hospital of Foshan, Guangdong Province, China
4Department of Otorhinolaryngology Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Thian-Sze Wong, email: [email protected]
Keywords: nasopharyngeal carcinoma, EBV, radiation sensitivity, MicroRNA BART7
Received: April 18, 2016 Accepted: January 10, 2017 Published: February 20, 2017
Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is very sensitive to radiotherapy. To date, the underlying mechanism remains poorly understood. Here, we demonstrated that expression of EBV-encoded microRNA BART7 (ebv-miR-BART7) increases responsiveness of NPC to radiation treatment by targeting GFPT1/TGFβ1 signaling. GFPT1 is the the key rate-limiting enzyme of the hexosamine signaling pathway and governs TGFβ1 production. TGFβ1, a pleotropic cytokine with the potency to trigger self-renewal and damage-repair machinery in somatic cells. TGFβ1 can protect zebrafish embryo from the lethal effects of radiation treatment. In silico analysis showed that ebv-miR-BART7 could target GFPT1 transcript. Correlation analysis on primary NPC tissues suggested that ebv-miR-BART7 and GFPT1 have negative expression correlation. Expression of GFPT1 and TGFβ1 were inducible by radiation in NPC cell with ebv-miR-BART7 expression. Further, suppressing endogenous GFPT1 expression inhibited TGFβ1 which subsequently increased the responsiveness of NPC to radiation treatment. Taken together, our results demonstrated that ebv-miR-BART7 controls TGFβ1 production by targeting GFPT1. Detection of ebv-miR-BART7 may provide useful indicator for monitoring NPC progression and predict therapeutic outcomes.
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