Epstein-Barr Virus EBER Transcripts Affect miRNA-Mediated Regulation of Specific Targets and Are Processed to Small RNA Species

Alles, Julia; Hasler, Daniele; Kazmi, Syed Mohammad Ali; Tesson, Mathias; Hamilton, Andrew J.; Schlegel, Linda; Marx, Stefanie; Eichner, Norbert; Reinhardt, Richard; Meister, Gunter; Wilson, Joanna B.; Grässer, Friedrich A.

doi:10.3390/ncrna1030170

Cited by 7 publications

(11 citation statements)

References 56 publications

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“…Significantly, EBER1/2 cooperated with BART16 in the specific down modulation of the S1PR1 3 0 UTR (P = 0.002). In conjunction with the previous report showing that BART16 had no effect on TOMM22 [28], this again illustrates that the effect of the EBERs are specific for a given miRNA vis-a-vis its mRNA target.…”

Section: Identification Of New Targets For Viral and Deregulated Hostsupporting

confidence: 84%

“…B). We have recently shown that coexpression of the EBV‐encoded EBER RNAs co‐represses certain targets such as down modulation of IL‐1α by miR‐142‐3p but had no effect on the regulation of TOMM22 by ebv‐miR‐BART16 . Expression of EBER1/2 also down modulated the empty vector and coexpression with BART16 increased this.…”

Section: Resultsmentioning

confidence: 99%

“…The ebv‐miR‐BART16 and EBER expression plasmids had been described previously . The miR‐148a precursor was cloned into pSG5 using the following oligonucleotides: 5′‐EcoRI‐miR‐148a: 5′‐CGG AAT TCT GTT GGG CAT TTG CTC CTG C‐3′, 3′‐BamHI‐miR‐148a: 5′‐CGC GGA TCC CAG TCA GGA GTC CAC CAG GG‐3′.…”

Section: Methodsmentioning

confidence: 99%

“…Total RNA from transfected HEK293T cells was extracted using peqGOLD Trifast (Peqlab, Erlangen, Germany) according to the manufacturer's description without washing steps. 20 μg RNA was separated on a 12% urea‐polyacrylamid gel and subsequently blotted onto a nylon membrane (Amersham, Freiburg, Germany) followed by chemical cross‐linking . After hybridization with UT 32 P‐labelled antisense probes (miRVana probe construction kit; Thermo Fisher (Ambion), Braunschweig, Germany) overnight and washing steps, the blots were exposed to phosphor screens and developed using a Typhoon Scanner (Amersham).…”

Section: Methodsmentioning

confidence: 99%

“…The EBER transcripts are expressed at up to 10 6 copies per cell in all EBV‐transformed tumours and cell lines . We have recently shown the EBERs exert an additional, miRNA‐specific down‐regulation on miRNA targets: co‐expression of the EBERs further down‐regulated the protein expression of interleukin 1α and RAC1 reporters by miR‐142‐3p and also the protein expression of interleukin 1α, but not of ADCY9, another known target of miR‐142‐3p . Further, the EBERs had no effect on the down‐regulation of TOMM22, a known target for the EBV‐encoded miRNA ebv‐miR‐BART16 .…”

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confidence: 96%

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miRNA expression profiling of Epstein–Barr virus‐associated NKTL cell lines by Illumina deep sequencing

et al. 2016

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The aim of this work was to establish the micro RNA profile of SNK 6 and SNT 16, two Epstein–Barr virus ( EBV )‐infected cell lines derived from nasal NK /T‐cell lymphoma ( NKTL ). The oncogenic EBV is strongly associated with the pathogenesis of nasal and extranodal NK /T‐cell lymphoma and expresses 44 mature micro RNA s and two noncoding EBV ‐encoded RNA s ( EBER s). mi RNA s are 19‐25nt noncoding RNA s that affect host and viral gene expression post‐transcriptionally. Deregulated mi RNA patterns are frequently linked to a variety of human cancers including lymphomas. mi RNA profiling of the two NK /T cell lines vs. primary cells revealed 10 and 4 up‐regulated and 10 and 12 down‐regulated mi RNA s in SNK 6 and SNT 16 cells respectively. The results were validated by qRT ‐ PCR for selected mi RNA s. Target gene analyses confirmed cullin 5 ( CUL 5) and sphingosin‐1‐phosphate receptor 1 (S1 PR 1) as targets for the down‐regulated hsa‐miR‐148a and viral ebv‐miR‐ BART 16 respectively. As recently demonstrated for the regulation of IL 1‐alpha by miR‐142‐3p, coexpression of the EBER s selectively exerted corepression of S1 PR 1 by BART 16 but not of CUL 5 by miR‐148a, indicating selective corepression by the EBER s.

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Section: Identification Of New Targets For Viral and Deregulated Hostsupporting

confidence: 84%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 96%

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miRNA expression profiling of Epstein–Barr virus‐associated NKTL cell lines by Illumina deep sequencing

et al. 2016

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Critical review of Epstein–Barr virus microRNAs relation with EBV‐associated gastric cancer

Zebardast

Tehrani

Latifi

et al. 2021

Journal Cellular Physiology

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Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is regarded as the most prevalent malignant tumor triggered by EBV infection. In recent years, increasing attention has been considered to recognize more about the disease process's exact mechanisms. There is accumulating evidence that showing epigenetic modifications play critical roles in the EBVaGC pathogenesis. MicroRNAs (miRNAs), as critical epigenetic modulators, are single-strand short noncoding RNA (length< 200 bp), which regulate gene expression through binding to the 3ʹ-untranslated region (3ʹ-UTR) of target RNA transcripts and either degrade or repress their activities. In the latest research on EBV, it was found that this virus could encode miRNAs. Mechanistically, EBV-encoded miRNAs are involved in carcinogenesis and the progression of EBV-associated malignancies. Moreover, these miRNAs implicated in immune evasion, identification of pattern recognition receptors, regulation of lymphocyte activation and lethality, modulation of infected host cell antigen, maintain of EBV infection status, promotion of cell proliferation, invasion and migration, and reduction of apoptosis. As good news, not only has recent data demonstrated the crucial function of EBV-encoded miRNAs in the pathogenesis of EBVaGC, but it has also been revealed that aberrant expression of exosomal miRNAs in EBVaGC has made them biomarkers for detection of EBVaGC. Regarding these substantial characterizes, the critical role of EBV-encoded miRNAs has been a hot topic in research. In this review, we will focus on the multiple mechanisms involved in EBVaGC caused by EBV-encoded miRNAs and briefly discuss their potential application in the clinic as a diagnostic biomarker.

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Analysis of the longitudinal stability of human plasma miRNAs and implications for disease biomarkers

Sandau,

Wiedrick,

McFarland

et al. 2024

Sci Rep

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There is great interest in developing clinical biomarker assays that can aid in non-invasive diagnosis and/or monitoring of human diseases, such as cancer, cardiovascular disease, and neurological diseases. Yet little is known about the longitudinal stability of miRNAs in human plasma. Here we assessed the intraindividual longitudinal stability of miRNAs in plasma from healthy human adults, and the impact of common factors (e.g., hemolysis, age) that may confound miRNA data. We collected blood by venipuncture biweekly over a 3-month period from 22 research participants who had fasted overnight, isolated total RNA, then performed miRNA qPCR. Filtering and normalization of the qPCR data revealed amplification of 134 miRNAs, 74 of which had high test–retest reliability and low percentage level drift, meaning they were stable in an individual over the 3-month time period. We also determined that, of nuisance factors, hemolysis and tobacco use have the greatest impact on miRNA levels and variance. These findings support that many miRNAs show intraindividual longitudinal stability in plasma from healthy human adults, including some reported as candidate biomarkers for Alzheimer’s disease.

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Epstein-Barr Virus EBER Transcripts Affect miRNA-Mediated Regulation of Specific Targets and Are Processed to Small RNA Species

Cited by 7 publications

References 56 publications

miRNA expression profiling of Epstein–Barr virus‐associated NKTL cell lines by Illumina deep sequencing

miRNA expression profiling of Epstein–Barr virus‐associated NKTL cell lines by Illumina deep sequencing

Critical review of Epstein–Barr virus microRNAs relation with EBV‐associated gastric cancer

Analysis of the longitudinal stability of human plasma miRNAs and implications for disease biomarkers

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