Editing of Epstein-Barr Virus-encoded BART6 MicroRNAs Controls Their Dicer Targeting and Consequently Affects Viral Latency*

Iizasa, Hisashi; Wulff, Bjorn-Erik; Alla, Nageswara R.; Maragkakis, Manolis; Megraw, Molly; Hatzigeorgiou, Artemis G.; Iwakiri, Dai; Takada, Kenzo; Wiedmer, Andreas; Showe, Louise C.; Lieberman, Paul M.; Nishikura, Kazuko

doi:10.1074/jbc.m110.138362

Cited by 217 publications

(234 citation statements)

References 68 publications

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“…Several genes involved in apoptosis, such as PUMA, BIM, and TOMM22, were identified as potential targets of various EBV miRNAs [32,33]. EBV BART miRNA targets, such as IPO7, Dicer, and LMP2A, participate in the immune evasion of NPC [31,34]. However, the biological effects and targets of EBV miRNAs have yet to be identified.…”

mentioning

confidence: 99%

Regulation network and expression profiles of Epstein-Barr virus-encoded microRNAs and their potential target host genes in nasopharyngeal carcinomas

Zeng

Huang

et al. 2014

Sci. China Life Sci.

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Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC) tumorigenesis. However, the mechanism(s) connecting EBV infection and NPC remain unclear. Recently, a new class of EBV microRNAs (miRNAs) has been described. To determine how EBV miRNAs control the expression of host genes, and to understand their potential role in NPC tumorigenesis, we profiled the expression of 44 mature EBV miRNAs and potential host genes in NPC and non-tumor nasopharyngeal epithelial tissues. We found that 40 EBV miRNAs from the BART transcript were highly expressed in NPC. Analysis of potential BART miRNA target genes revealed that 3140 genes and several important pathways might be involved in the carcinogenesis of NPC. A total of 105 genes with potential EBV miRNA binding sites were significantly downregulated, suggesting that EBV miRNAs may regulate these genes and contribute to NPC carcinogenesis. An EBV miRNA and host gene regulation network was generated to provide useful clues for validating of EBV miRNA functions in NPC tumorigenesis.

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mentioning

confidence: 99%

Regulation network and expression profiles of Epstein-Barr virus-encoded microRNAs and their potential target host genes in nasopharyngeal carcinomas

Zeng

Huang

et al. 2014

Sci. China Life Sci.

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“…Further investigation of potential EBV miRNA target genes revealed the inhibition of tumor suppressor genes, such as PTEN, and the extensive dysregulation of several pathways that are commonly involved in NPC, such as Wnt signaling. In HeLa cells transfected with miR-BART6-5p RNAs, which is EBV-encoded, the expression of miR-205-5p was increased more than 2-fold (Iizasa et al, 2010). In the current study, miR-205-5p expression was considerably higher in NPC tissues relative to control samples.…”

Section: Discussionmentioning

confidence: 99%

Five miRNAs as Novel Diagnostic Biomarker Candidates for Primary Nasopharyngeal Carcinoma

Tang¹,

Zhong²,

Li³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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MicroRNAs (miRNAs) play an essential role in the development and progression of nasopharyngeal carcinomas (NPC). Despite advances in the field of cancer molecular biology and biomarker discovery, the development of clinically validated biomarkers for primary NPC has remained elusive. In this study, we investigated the expression and clinical significance of miRNAs as novel primary NPC diagnostic biomarkers. We used an array containing 2, 500 miRNAs to identify 22 significant miRNAs, and these candidate miRNAs were validated using 67 fresh NPC and 25 normal control tissues via quantitative real-time PCR (qRT-PCR). Expression and correlation analyses were performed with various statistical approaches, in addition to logistic regression and receiver operating characteristic curve analyses to evaluate diagnostic efficacy. qRT-PCR revealed five differentially expressed miRNAs (miR-93-5p, miR-135b-5p, miR-205-5p and miR-183-5p) in NPC tissue samples relative to control samples (p<0.05), with miR-135b-5p and miR-205-5p being of significant diagnostic value (p<0.01). Moreover, comparison of NPC patient clinicopathologic data revealed a negative correlation between miR-93-5p and miR-183-5p expression levels and lymph node status (p<0.05). These findings display an altered expression of many miRNAs in NPC tissues, thus providing information pertinent to pathophysiological and diagnostic research. Ultimately, miR-135b-5p and miR-205-5p may be implicated as novel NPC candidate biomarkers, while miR-93-5p, miR-650 and miR-183-5p may find application as relevant clinical pathology and diagnostic candidate biomarkers.

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“…First, the editing will affect miRNA loading into miRISC (Figure 3). Several editing sites were found in the Epstein Barr Virus-encoded pri-miRNAs in latently EBV-infected cells, and editing suppressed the miRISC loading of miR-BART6-5p [105]. Therefore, it may also affect the miRISC loading of endogenous miRNAs.…”

Section: Editing In Small Non-coding Rnasmentioning

confidence: 99%

ADAR-mediated RNA editing in non-coding RNA sequences

Yang

Zhou

Jin

2013

Sci. China Life Sci.

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Adenosine to inosine (A-to-I) RNA editing is the most abundant editing event in animals. It converts adenosine to inosine in double-stranded RNA regions through the action of the adenosine deaminase acting on RNA (ADAR) proteins. Editing of pre-mRNA coding regions can alter the protein codon and increase functional diversity. However, most of the A-to-I editing sites occur in the non-coding regions of pre-mRNA or mRNA and non-coding RNAs. Untranslated regions (UTRs) and introns are located in pre-mRNA non-coding regions, thus A-to-I editing can influence gene expression by nuclear retention, degradation, alternative splicing, and translation regulation. Non-coding RNAs such as microRNA (miRNA), small interfering RNA (siRNA) and long non-coding RNA (lncRNA) are related to pre-mRNA splicing, translation, and gene regulation. A-to-I editing could therefore affect the stability, biogenesis, and target recognition of non-coding RNAs. Finally, it may influence the function of non-coding RNAs, resulting in regulation of gene expression. This review focuses on the function of ADAR-mediated RNA editing on mRNA non-coding regions (UTRs and introns) and non-coding RNAs (miRNA, siRNA, and lncRNA).

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Editing of Epstein-Barr Virus-encoded BART6 MicroRNAs Controls Their Dicer Targeting and Consequently Affects Viral Latency*

Cited by 217 publications

References 68 publications

Regulation network and expression profiles of Epstein-Barr virus-encoded microRNAs and their potential target host genes in nasopharyngeal carcinomas

Regulation network and expression profiles of Epstein-Barr virus-encoded microRNAs and their potential target host genes in nasopharyngeal carcinomas

Five miRNAs as Novel Diagnostic Biomarker Candidates for Primary Nasopharyngeal Carcinoma

ADAR-mediated RNA editing in non-coding RNA sequences

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