Evidence map›Paper›PMID 26024393›Full record

ArticleCell death and differentiation2016

Comprehensive identification of genes driven by ERV9-LTRs reveals TNFRSF10B as a re-activatable mediator of testicular cancer cell death.

U Beyer, S K Krönung, A Leha, L Walter, M Dobbelstein

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death and differentiation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

32 citing papers in PubMed, 40 citations in OpenAlex.

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  12. Human Endogenous Retroviruses in Diseases.Sub-cellular biochemistry · 2023
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  20. Human endogenous retroviruses in development and disease.Computational and structural biotechnology journal · 2021
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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

5 authors at 2 institutions in 1 country.

U BeyerInstitute of Molecular Oncology, Göttingen Center of Molecular Biosciences (GZMB), University of Göttingen, Göttingen, D-37077, Germany.
S K KrönungInstitute of Molecular Oncology, Göttingen Center of Molecular Biosciences (GZMB), University of Göttingen, Göttingen, D-37077, Germany.
A LehaDepartment of Medical Statistics, University Göttingen, Göttingen, D-37033, Germany.
L WalterPrimate Genetics Laboratory, German Primate Center, Göttingen, D-37077, Germany.
M DobbelsteinInstitute of Molecular Oncology, Göttingen Center of Molecular Biosciences (GZMB), University of Göttingen, Göttingen, D-37077, Germany.
University of Göttingen · DEGerman Primate Center · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The long terminal repeat (LTR) of human endogenous retrovirus type 9 (ERV9) acts as a germline-specific promoter that induces the expression of a proapoptotic isoform of the tumor suppressor homologue p63, GTAp63, in male germline cells. Testicular cancer cells silence this promoter, but inhibitors of histone deacetylases (HDACs) restore GTAp63 expression and give rise to apoptosis. We show here that numerous additional transcripts throughout the genome are driven by related ERV9-LTRs. 3' Rapid amplification of cDNA ends (3'RACE) was combined with next-generation sequencing to establish a large set of such mRNAs. HDAC inhibitors induce these ERV9-LTR-driven genes but not the LTRs from other ERVs. In particular, a transcript encoding the death receptor DR5 originates from an ERV9-LTR inserted upstream of the protein coding regions of the TNFRSF10B gene, and it shows an expression pattern similar to GTAp63. When treating testicular cancer cells with HDAC inhibitors as well as the death ligand TNF-related apoptosis-inducing ligand (TRAIL), rapid cell death was observed, which depended on TNFRSF10B expression. HDAC inhibitors also cooperate with cisplatin (cDDP) to promote apoptosis in testicular cancer cells. ERV9-LTRs not only drive a large set of human transcripts, but a subset of them acts in a proapoptotic manner. We propose that this avoids the survival of damaged germ cells. HDAC inhibition represents a strategy of restoring the expression of a class of ERV9-LTR-mediated genes in testicular cancer cells, thereby re-enabling tumor suppression.

Indexed as

ApoptosisCell Line, TumorCisplatinEndogenous RetrovirusesGene Expression Regulation, NeoplasticGerm CellsHistone Deacetylase InhibitorsHistone DeacetylasesHumansMalePromoter Regions, GeneticProtein IsoformsReceptors, TNF-Related Apoptosis-Inducing LigandReceptors, Tumor Necrosis FactorRNA, MessengerTerminal Repeat SequencesCisplatinHistone Deacetylase InhibitorsHistone DeacetylasesProtein IsoformsReceptors, TNF-Related Apoptosis-Inducing LigandReceptors, Tumor Necrosis FactorRNA, MessengerTNFRSF10B protein, humanTNFRSF21 protein, humanTP63 protein, humanTranscription FactorsTumor Suppressor Proteins

Identifiers

PMID26024393
PMCPMC4815979
OpenAlexW1537164477

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.