Evidence map›Paper›PMID 29036465›Full record

ArticleNucleic acids research2017

hnRNPM guides an alternative splicing program in response to inhibition of the PI3K/AKT/mTOR pathway in Ewing sarcoma cells.

Ilaria Passacantilli, Paola Frisone, Elisa De Paola, Marco Fidaleo, Maria Paola Paronetto

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
3.1field-weighted citation impact, top 7% 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

48 citing papers in PubMed, 79 citations in OpenAlex.

  1. Article
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  4. Review
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  8. Article
  9. HnRNPM modulates alternative splicing in germ cells by recruiting PTBP1.Reproductive biology and endocrinology : RB&E · 2025
    Article
  10. Review
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  20. Cancers · 2022
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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 1 institution in 1 country.

Ilaria PassacantilliLaboratory of Cellular and Molecular Neurobiology, Fondazione Santa Lucia, Via del Fosso di Fiorano, 64, 00143 Rome, Italy.
Paola FrisoneLaboratory of Cellular and Molecular Neurobiology, Fondazione Santa Lucia, Via del Fosso di Fiorano, 64, 00143 Rome, Italy.
Elisa De PaolaLaboratory of Cellular and Molecular Neurobiology, Fondazione Santa Lucia, Via del Fosso di Fiorano, 64, 00143 Rome, Italy.
Marco FidaleoLaboratory of Cellular and Molecular Neurobiology, Fondazione Santa Lucia, Via del Fosso di Fiorano, 64, 00143 Rome, Italy.
Maria Paola ParonettoLaboratory of Cellular and Molecular Neurobiology, Fondazione Santa Lucia, Via del Fosso di Fiorano, 64, 00143 Rome, Italy.
Fondazione Santa Lucia · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ewing sarcomas (ES) are biologically aggressive tumors of bone and soft tissues for which no cure is currently available. Most ES patients do not respond to chemotherapeutic treatments or acquire resistance. Since the PI3K/AKT/mTOR axis is often deregulated in ES, its inhibition offers therapeutic perspective for these aggressive tumors. Herein, by using splicing sensitive arrays, we have uncovered an extensive splicing program activated upon inhibition of the PI3K/AKT/mTOR signaling pathway by BEZ235. Bioinformatics analyses identified hnRNPM as a key factor in this response. HnRNPM motifs were significantly enriched in introns flanking the regulated exons and proximity of binding represented a key determinant for hnRNPM-dependent splicing regulation. Knockdown of hnRNPM expression abolished a subset of BEZ235-induced splicing changes that contained hnRNPM binding sites, enhanced BEZ235 cytotoxicity and limited the clonogenicity of ES cells. Importantly, hnRNPM up-regulation correlates with poor outcome in sarcoma patients. These findings uncover an hnRNPM-dependent alternative splicing program set in motion by inhibition of the mTOR/AKT/PI3K pathway in ES cells that limits therapeutic efficacy of pharmacologic inhibitors, suggesting that combined inhibition of the PI3K/AKT/mTOR pathway and hnRNPM activity may represent a novel approach for ES treatment.

Indexed as

Alternative SplicingAntineoplastic AgentsBone NeoplasmsCell LineExonsHeterogeneous-Nuclear Ribonucleoprotein Group MHumansImidazolesNucleotide MotifsPhosphoinositide-3 Kinase InhibitorsProto-Oncogene Proteins c-aktQuinolinesSarcoma, EwingSignal TransductionTOR Serine-Threonine KinasesTranscriptomeAntineoplastic AgentsdactolisibHeterogeneous-Nuclear Ribonucleoprotein Group MHNRNPM protein, humanImidazolesPhosphoinositide-3 Kinase InhibitorsProto-Oncogene Proteins c-aktQuinolinesTOR Serine-Threonine Kinases

Identifiers

PMID29036465
PMCPMC5716164
OpenAlexW2763234678

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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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.