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KMID : 0939920200520020492
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대한암학회지
2020 Volume.52 No. 2 p.492 ~ p.504
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EBV-miR-BHRF1-1 Targets p53 Gene: Potential Role in Epstein-Barr Virus Associated Chronic Lymphocytic Leukemia
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Xu Dan-Min
Kong Yi-Lin
Wang Li
Zhu Hua-Yuan
Wu Jia-Zhu
Xia Yi
Li Yue
Qin Shu-Chao
Fan Lei
Li Jian-Yong
Liang Jin-Hua
Xu Wei
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Abstract
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Purpose: The purpose of this study was to investigate the prognostic impact of Epstein-Barr virus (EBV)?microRNA (miRNA, miR)-BHRF1-1 with chronic lymphocytic leukemia (CLL) as well as role of EBV-miR-BHRF1-1 in p53 gene.
Materials and Methods: Quantitative reverse transcription?polymerase chain reaction and western blotting were used to quantify EBV-miR-BHRF1-1 and p53 expression in cultured CLL.
Results: p53 aberration was associated with the higher expression level of EBV-miR-BHRF1-1 (p < 0.001) which was also an independent prognostic marker for overall survival (p=0.028; hazard ratio, 5.335; 95% confidence interval, 1.193 to 23.846) in 97 newly-diagnosed CLL patients after adjusted with International Prognostic Index for patients with CLL. We identified EBV-miR-BHRF1-1 as a viral miRNA regulator of p53. EBV-miR-BHRF1-1 repressed luciferase reporter activity by specific interaction with the seed region within the p53 3′-untranslated region. Discordance of p53 messenger RNA and protein expression was associated with high EBV-miR-BHRF1-1 levels in CLL patients and cell lines. EBV-miR-BHRF1-1 inhibition upregulated p53 protein expression, induced cell cycle arrest and apoptosis and decreased cell proliferation in cell lines. EBV-miR-BHRF1-1 mimics downregulated p53 protein expression, decreased cell cycle arrest and apoptosis, and induced cell proliferation in cell lines.
Conclusion: This study supported the role of EBV-miR-BHRF1-1 in p53 regulation in vitro. Our results support the potential of EBV-miR-BHRF1-1 as a therapeutic target in EBV-associated CLL with p53 gene aberration.
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KEYWORD
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Chronic lymphocytic leukemia, EBV-miR-BHRF1-1, p53
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