Evidence map›Paper›PMID 32545483›Full record

ArticleInternational journal of molecular sciences2020

Silencing Core Spliceosome Sm Gene Expression Induces a Cytotoxic Splicing Switch in the Proteasome Subunit Beta 3 mRNA in Non-Small Cell Lung Cancer Cells.

Maxime Blijlevens, Malgorzata A Komor, Rocco Sciarrillo, Egbert F Smit, Remond J A Fijneman, Victor W van Beusechem

Open access · goldAbstract readComparative Study
In one paragraph

Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.0field-weighted citation impact, top 25% 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

13 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Non-targeting control for MISSION shRNA library silencesMolecular therapy. Nucleic acids · 2021
    Article
  11. Article
  12. Review
  13. Article
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 2 institutions in 1 country.

Maxime BlijlevensAmsterdam UMC, Medical Oncology, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
Malgorzata A KomorAmsterdam UMC, Medical Oncology, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
Rocco SciarrilloAmsterdam UMC, Medical Oncology, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
Egbert F SmitDepartment of Thoracic Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Remond J A FijnemanDepartment of Pathology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.ORCID 0000-0003-2076-5521
Victor W van BeusechemAmsterdam UMC, Medical Oncology, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
Amsterdam University Medical Centers · NLThe Netherlands Cancer Institute · NL

Funding

Stichting VUmc-CCA -Walter Bruckerhoff Stiftung -
6 · The paper itself

Abstract

The core spliceosomal Sm proteins were recently proposed as cancer-selective lethal targets in non-small cell lung cancer (NSCLC). In contrast, the loss of the commonly mutated cancer target SF3B1 appeared to be toxic to non-malignant cells as well. In the current study, the transcriptomes of A549 NSCLC cells, in which SF3B1 or SNRPD3 was silenced, were compared using RNA sequencing. The skipping of exon 4 of the proteasomal subunit beta type-3 (PSMB3) mRNA, resulting in a shorter PSMB3-S variant, occurred only after silencing SNRPD3. This observation was extended to the other six Sm genes. Remarkably, the alternative splicing of PSMB3 mRNA upon Sm gene silencing was not observed in non-malignant IMR-90 lung fibroblasts. Furthermore, PSMB3 was found to be overexpressed in NSCLC clinical samples and PSMB3 expression correlated with Sm gene expression. Moreover, a high PSMB3 expression corresponds to worse survival in patients with lung adenocarcinomas. Finally, silencing the canonical full-length PSMB3-L, but not the shorter PSMB3-S variant, was cytotoxic and was accompanied by a decrease in proteasomal activity. Together, silencing Sm genes, but not SF3B1, causes a cytotoxic alternative splicing switch in the PSMB3 mRNA in NSCLC cells only.

Indexed as

A549 CellsAlternative SplicingCarcinoma, Non-Small-Cell LungDown-RegulationExonsGene Expression ProfilingGene Expression Regulation, NeoplasticGene SilencingHumansLung NeoplasmsNonsense Mediated mRNA DecayPhosphoproteinsProteasome Endopeptidase ComplexRNA Splicing FactorsSequence Analysis, RNAsnRNP Core ProteinsPhosphoproteinsProteasome Endopeptidase ComplexRNA Splicing FactorsSF3B1 protein, humansnRNP Core ProteinsSNRPD3 protein, humanalternative splicingnon-small cell lung cancerproteasomeSm proteins

Identifiers

PMID32545483
PMCPMC7349683
OpenAlexW3035347113

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.