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Comprehensive profiling of Epstein-Barr virus-encoded miRNA species associated with specific latency types in tumor cells.

Yang HJ, Huang TJ, Yang CF, Peng LX, Liu RY, Yang GD, Chu QQ, Huang JL, Liu N, Huang HB, Zhu ZY, Qian CN, Huang BJ - Virol. J. (2013)

Bottom Line: EBV expresses different genes that are associated with three latency types.Specifically, in nasopharyngeal carcinoma (NPC) tissues and the EBV-positive cell line C666-1, the miR-BART family accounted for more than 10% of all detected miRNAs, suggesting that these miRNAs have important roles in maintaining latent EBV infections and in driving NPC tumorigenesis.In addition, EBV miRNA-based clustering analysis clearly distinguished between the three distinct EBV latency types, and our results suggested that a switch from type I to type III latency might occur in the Daudi BL cell line.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China. qianchn@sysucc.org.cn.

ABSTRACT

Background: Epstein-Barr virus (EBV) is an etiological cause of many human lymphocytic and epithelial malignancies. EBV expresses different genes that are associated with three latency types. To date, as many as 44 EBV-encoded miRNA species have been found, but their comprehensive profiles in the three types of latent infection that are associated with various types of tumors are not well documented.

Methods: In the present study, we utilized poly (A)-tailed quantitative real-time RT-PCR in combination with microarray analysis to measure the relative abundances of viral miRNA species in a subset of representative lymphoid and epithelial tumor cells with various EBV latency types.

Results: Our findings showed that the miR-BHRF1 and miR-BART families were expressed differentially in a tissue- and latency type-dependent manner. Specifically, in nasopharyngeal carcinoma (NPC) tissues and the EBV-positive cell line C666-1, the miR-BART family accounted for more than 10% of all detected miRNAs, suggesting that these miRNAs have important roles in maintaining latent EBV infections and in driving NPC tumorigenesis. In addition, EBV miRNA-based clustering analysis clearly distinguished between the three distinct EBV latency types, and our results suggested that a switch from type I to type III latency might occur in the Daudi BL cell line.

Conclusions: Our data provide a comprehensive profiling of the EBV miRNA transcriptome that is associated with specific tumor cells in the three types of latent EBV infection states. EBV miRNA species represent a cluster of non-encoding latency biomarkers that are differentially expressed in tumor cells and may help to distinguish between the different latency types.

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Related in: MedlinePlus

Genomic locations of all viral miRNA species. The top panel shows the position of latent genes and promoters (pennants). The middle panel shows the position of the EBV miRNAs, including the miR-BHRF1 and miR-BART families. The promoters of the BHRF1 and BART families are marked with pennants, and the EBV miRNA species whose genes are located within the deletion region in the prototype, B95-8-derived strain are shown in the lower panel. The locations of EBV miRNA genes are listed in genomic order from miRBase.
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Figure 1: Genomic locations of all viral miRNA species. The top panel shows the position of latent genes and promoters (pennants). The middle panel shows the position of the EBV miRNAs, including the miR-BHRF1 and miR-BART families. The promoters of the BHRF1 and BART families are marked with pennants, and the EBV miRNA species whose genes are located within the deletion region in the prototype, B95-8-derived strain are shown in the lower panel. The locations of EBV miRNA genes are listed in genomic order from miRBase.

Mentions: The previous identification of the EBV latency types was mainly based on viral EBERs, nuclear antigens, LMP1, LMP2 and the Bam H1 rightward transcripts [2,22-25]. EBNA1 is expressed under the alternative promoters Wp, Cp and Qp in a latency type-specific manner [22,24,35], and LMP1 exhibits differential abundance when compared to the various latency types [1], suggesting that the activities of the three latency promoters that control EBNA1 expression and LMP1 abundance can characterize the three latency types. The essential latency characteristics described above are partially illustrated in FigureĀ 1. In the present study, we measured the activities of the Cp/Qp/Wp promoters and the expression level of LMP1 to characterize the different types of latent EBV infections.


Comprehensive profiling of Epstein-Barr virus-encoded miRNA species associated with specific latency types in tumor cells.

Yang HJ, Huang TJ, Yang CF, Peng LX, Liu RY, Yang GD, Chu QQ, Huang JL, Liu N, Huang HB, Zhu ZY, Qian CN, Huang BJ - Virol. J. (2013)

Genomic locations of all viral miRNA species. The top panel shows the position of latent genes and promoters (pennants). The middle panel shows the position of the EBV miRNAs, including the miR-BHRF1 and miR-BART families. The promoters of the BHRF1 and BART families are marked with pennants, and the EBV miRNA species whose genes are located within the deletion region in the prototype, B95-8-derived strain are shown in the lower panel. The locations of EBV miRNA genes are listed in genomic order from miRBase.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231337&req=5

Figure 1: Genomic locations of all viral miRNA species. The top panel shows the position of latent genes and promoters (pennants). The middle panel shows the position of the EBV miRNAs, including the miR-BHRF1 and miR-BART families. The promoters of the BHRF1 and BART families are marked with pennants, and the EBV miRNA species whose genes are located within the deletion region in the prototype, B95-8-derived strain are shown in the lower panel. The locations of EBV miRNA genes are listed in genomic order from miRBase.
Mentions: The previous identification of the EBV latency types was mainly based on viral EBERs, nuclear antigens, LMP1, LMP2 and the Bam H1 rightward transcripts [2,22-25]. EBNA1 is expressed under the alternative promoters Wp, Cp and Qp in a latency type-specific manner [22,24,35], and LMP1 exhibits differential abundance when compared to the various latency types [1], suggesting that the activities of the three latency promoters that control EBNA1 expression and LMP1 abundance can characterize the three latency types. The essential latency characteristics described above are partially illustrated in FigureĀ 1. In the present study, we measured the activities of the Cp/Qp/Wp promoters and the expression level of LMP1 to characterize the different types of latent EBV infections.

Bottom Line: EBV expresses different genes that are associated with three latency types.Specifically, in nasopharyngeal carcinoma (NPC) tissues and the EBV-positive cell line C666-1, the miR-BART family accounted for more than 10% of all detected miRNAs, suggesting that these miRNAs have important roles in maintaining latent EBV infections and in driving NPC tumorigenesis.In addition, EBV miRNA-based clustering analysis clearly distinguished between the three distinct EBV latency types, and our results suggested that a switch from type I to type III latency might occur in the Daudi BL cell line.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China. qianchn@sysucc.org.cn.

ABSTRACT

Background: Epstein-Barr virus (EBV) is an etiological cause of many human lymphocytic and epithelial malignancies. EBV expresses different genes that are associated with three latency types. To date, as many as 44 EBV-encoded miRNA species have been found, but their comprehensive profiles in the three types of latent infection that are associated with various types of tumors are not well documented.

Methods: In the present study, we utilized poly (A)-tailed quantitative real-time RT-PCR in combination with microarray analysis to measure the relative abundances of viral miRNA species in a subset of representative lymphoid and epithelial tumor cells with various EBV latency types.

Results: Our findings showed that the miR-BHRF1 and miR-BART families were expressed differentially in a tissue- and latency type-dependent manner. Specifically, in nasopharyngeal carcinoma (NPC) tissues and the EBV-positive cell line C666-1, the miR-BART family accounted for more than 10% of all detected miRNAs, suggesting that these miRNAs have important roles in maintaining latent EBV infections and in driving NPC tumorigenesis. In addition, EBV miRNA-based clustering analysis clearly distinguished between the three distinct EBV latency types, and our results suggested that a switch from type I to type III latency might occur in the Daudi BL cell line.

Conclusions: Our data provide a comprehensive profiling of the EBV miRNA transcriptome that is associated with specific tumor cells in the three types of latent EBV infection states. EBV miRNA species represent a cluster of non-encoding latency biomarkers that are differentially expressed in tumor cells and may help to distinguish between the different latency types.

Show MeSH
Related in: MedlinePlus