Evidence map›Paper›PMID 25942495›Full record

ArticlePloS one2015

Next-Generation Sequencing Analysis Reveals Differential Expression Profiles of MiRNA-mRNA Target Pairs in KSHV-Infected Cells.

Coralie Viollet, David A Davis, Martin Reczko, Joseph M Ziegelbauer, Francesco Pezzella, Jiannis Ragoussis, Robert Yarchoan

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.3field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 22 citations in OpenAlex.

  1. Review
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  4. IFN-I inducibleFrontiers in immunology · 2022
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 6 institutions in 4 countries.

Coralie ViolletHIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America; The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
David A DavisHIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
Martin ReczkoInstitute of Molecular Oncology, Alexander Fleming Biomedical Sciences Research Center, Vari, Greece.
Joseph M ZiegelbauerHIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
Francesco PezzellaNuffield Division of Clinical Laboratory Sciences, University of Oxford, Oxford, United Kingdom.
Jiannis RagoussisThe Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Institute of Molecular Oncology, Alexander Fleming Biomedical Sciences Research Center, Vari, Greece; McGill University and Génome Québec Innovation Centre, Montréal, Canada.
Robert YarchoanHIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
Center for Cancer Research · USAlexander Fleming Biomedical Sciences Research Center · GRCentre for Human Genetics · GBNational Cancer Institute · USNational Institutes of Health · USUniversity of Oxford · GB

Funding

Study of Tumor Pathogenesis and Development of Therapies for AIDS MalignanciesZIABC010885 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI YARCHOAN, ROBERT · 2009 to 2025
$15.7M
Functions of KSHV microRNAs and circular RNAsZIABC011176 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ZIEGELBAUER, JOSEPH · 2009 to 2025
$14.0M
Intramural NIH HHSWellcome TrustWellcome Trust 095493
6 · The paper itself

Abstract

Kaposi's sarcoma associated herpesvirus (KSHV) causes several tumors, including primary effusion lymphoma (PEL) and Kaposi's sarcoma (KS). Cellular and viral microRNAs (miRNAs) have been shown to play important roles in regulating gene expression. A better knowledge of the miRNA-mediated pathways affected by KSHV infection is therefore important for understanding viral infection and tumor pathogenesis. In this study, we used deep sequencing to analyze miRNA and cellular mRNA expression in a cell line with latent KSHV infection (SLKK) as compared to the uninfected SLK line. This approach revealed 153 differentially expressed human miRNAs, eight of which were independently confirmed by qRT-PCR. KSHV infection led to the dysregulation of ~15% of the human miRNA pool and most of these cellular miRNAs were down-regulated, including nearly all members of the 14q32 miRNA cluster, a genomic locus linked to cancer and that is deleted in a number of PEL cell lines. Furthermore, we identified 48 miRNAs that were associated with a total of 1,117 predicted or experimentally validated target mRNAs; of these mRNAs, a majority (73%) were inversely correlated to expression changes of their respective miRNAs, suggesting miRNA-mediated silencing mechanisms were involved in a number of these alterations. Several dysregulated miRNA-mRNA pairs may facilitate KSHV infection or tumor formation, such as up-regulated miR-708-5p, associated with a decrease in pro-apoptotic caspase-2 and leukemia inhibitory factor LIF, or down-regulated miR-409-5p, associated with an increase in the p53-inhibitor MDM2. Transfection of miRNA mimics provided further evidence that changes in miRNAs are driving some observed mRNA changes. Using filtered datasets, we also identified several canonical pathways that were significantly enriched in differentially expressed miRNA-mRNA pairs, such as the epithelial-to-mesenchymal transition and the interleukin-8 signaling pathways. Overall, our data provide a more detailed understanding of KSHV latency and guide further studies of the biological significance of these changes.

Indexed as

Base SequenceCell Line, TumorEpithelial-Mesenchymal TransitionHerpesvirus 8, HumanHigh-Throughput Nucleotide SequencingHumansInterleukin-8Lymphoma, Primary EffusionMicroRNAsProto-Oncogene Proteins c-mdm2RNA, MessengerSarcoma, KaposiSequence Analysis, DNATumor Suppressor Protein p53CXCL8 protein, humanInterleukin-8MDM2 protein, humanMicroRNAsMIRN409 microRNA, humanMIRN708 microRNA, humanProto-Oncogene Proteins c-mdm2RNA, MessengerTumor Suppressor Protein p53

Identifiers

PMID25942495
PMCPMC4420468
OpenAlexW256445470

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.