期刊
ONCOTARGET
卷 8, 期 12, 页码 20297-20308出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.15526
关键词
nasopharyngeal carcinoma; EBV; radiation sensitivity; MicroRNA BART7
资金
- National Natural Science Foundation of China [81302376, 01121626, JCYJ20140903112959960]
- S. K. Yee Medical Foundation Grant
- University of Hong Kong [201311159124, 201411159165]
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/TGFa1 signaling. GFPT1 is the the key rate-limiting enzyme of the hexosamine signaling pathway and governs TGF beta 1 production. TGF beta 1, a pleotropic cytokine with the potency to trigger self-renewal and damage-repair machinery in somatic cells. TGF beta 1 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 TGF beta 1 were inducible by radiation in NPC cell with ebv-miR-BART7 expression. Further, suppressing endogenous GFPT1 expression inhibited TGF beta 1 which subsequently increased the responsiveness of NPC to radiation treatment. Taken together, our results demonstrated that ebv-miR-BART7 controls TGF beta 1 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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