Evidence map›Paper›PMID 26450900›Full record

ArticleOncotarget2015

Genotoxic stress inhibits Ewing sarcoma cell growth by modulating alternative pre-mRNA processing of the RNA helicase DHX9.

Marco Fidaleo, Francesca Svetoni, Elisabetta Volpe, Belén Miñana, Daniela Caporossi, Maria Paola Paronetto

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

33 citing papers in PubMed, 44 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
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  7. An impaired splicing program underlies differentiation defects in hSOD1Cellular and molecular life sciences : CMLS · 2023
    Article
  8. Article
  9. Article
  10. Cancers · 2022
    Article
  11. Secondary structures in RNA synthesis, splicing and translation.Computational and structural biotechnology journal · 2022
    Review
  12. Article
  13. Article
  14. Article
  15. RNA Helicases as Shadow Modulators of Cell Cycle Progression.International journal of molecular sciences · 2021
    Review
  16. Review
  17. Article
  18. Review
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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

6 authors at 3 institutions in 2 countries.

Marco FidaleoDepartment of Movement, Human and Health Sciences, University of Rome "Foro Italico", Rome, Italy.
Francesca SvetoniDepartment of Movement, Human and Health Sciences, University of Rome "Foro Italico", Rome, Italy.
Elisabetta VolpeLaboratories of Cellular and Molecular Neurobiology and of Neuroimmunology, CERC, Fondazione Santa Lucia, Rome, Italy.
Belén MiñanaCentre de Regulació Genòmica, Barcelona, Spain.
Daniela CaporossiDepartment of Movement, Human and Health Sciences, University of Rome "Foro Italico", Rome, Italy.
Maria Paola ParonettoDepartment of Movement, Human and Health Sciences, University of Rome "Foro Italico", Rome, Italy.
Fondazione Santa Lucia · ITForo Italico University of Rome · ITCentre for Genomic Regulation · ES

Funding

Worldwide Cancer Research 14-0333
6 · The paper itself

Abstract

Alternative splicing plays a key role in the DNA damage response and in cancer. Ewing Sarcomas (ES) are aggressive tumors caused by different chromosomal translocations that yield in-frame fusion proteins driving transformation. RNA profiling reveals genes differentially regulated by UV light irradiation in two ES cell lines exhibiting different sensitivity to genotoxic stress. In particular, irradiation induces a new isoform of the RNA helicase DHX9 in the more sensitive SK-N-MC cells, which is targeted to nonsense-mediated decay (NMD), causing its downregulation. DHX9 protein forms a complex with RNA polymerase II (RNAPII) and EWS-FLI1 to enhance transcription. Silencing of DHX9 in ES cells sensitizes them to UV treatment and impairs recruitment of EWS-FLI1 to target genes, whereas DHX9 overexpression protects ES cells from genotoxic stress. Mechanistically, we found that UV light irradiation leads to enhanced phosphorylation and decreased processivity of RNAPII in SK-N-MC cells, which in turn causes inclusion of DHX9 exon 6A. A similar effect on DHX9 splicing was also elicited by treatment with the chemotherapeutic drug etoposide, indicating a more general mechanism of regulation in response to DNA damage. Our data identify a new NMD-linked splicing event in DHX9 with impact on EWS-FLI1 oncogenic activity and ES cell viability.

Indexed as

Alternative SplicingCell ProliferationDNA DamageBone NeoplasmsCell Line, TumorCell SurvivalDEAD-box RNA HelicasesEtoposideGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticHumansNeoplasm ProteinsOncogene Proteins, FusionPhosphorylationProto-Oncogene Protein c-fli-1RNA-Binding Protein EWSDEAD-box RNA HelicasesDHX9 protein, humanEtoposideEWS-FLI fusion proteinNeoplasm ProteinsOncogene Proteins, FusionProto-Oncogene Protein c-fli-1RNA-Binding Protein EWSRNA, MessengerRNA Polymerase IIRNA PrecursorsTopoisomerase II Inhibitorsalternative splicingDHX9DNA damageEwing sarcoma

Identifiers

PMID26450900
PMCPMC4741636
OpenAlexW2179429226

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.