Evidence map›Paper›PMID 30705407›Full record

ArticleOncogene2019

High-throughput RNAi screening reveals cancer-selective lethal targets in the RNA spliceosome.

Maxime Blijlevens, Ida H van der Meulen-Muileman, Renée X de Menezes, Egbert F Smit, Victor W van Beusechem

Open access · greenAbstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

18 citing papers in PubMed, 28 citations in OpenAlex.

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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 3 institutions in 1 country.

Maxime BlijlevensAmsterdam UMC, Vrije Universiteit Amsterdam, Medical Oncology, Cancer Center Amsterdam, de Boelelaan 1118, Amsterdam, The Netherlands.
Ida H van der Meulen-MuilemanAmsterdam UMC, Vrije Universiteit Amsterdam, Medical Oncology, Cancer Center Amsterdam, de Boelelaan 1118, Amsterdam, The Netherlands.
Renée X de MenezesAmsterdam UMC, Vrije Universiteit Amsterdam, Epidemiology and Biostatistics, Netherlands Bioinformatics Center, de Boelelaan 1118, Amsterdam, The Netherlands.
Egbert F SmitDepartment of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Victor W van BeusechemAmsterdam UMC, Vrije Universiteit Amsterdam, Medical Oncology, Cancer Center Amsterdam, de Boelelaan 1118, Amsterdam, The Netherlands. vw.vanbeusechem@vumc.nl.
Vrije Universiteit Amsterdam · NLAmsterdam University Medical Centers · NLThe Netherlands Cancer Institute · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Novel therapeutic strategies for non-small-cell lung cancer (NSCLC) are urgently needed. RNA splicing, orchestrated by the spliceosome, is deregulated in many forms of cancer, including NSCLC. Here, we performed high-throughput screening with a small interfering RNA library targeting all annotated human spliceosome proteins to identify cancer-selective lethal targets in the RNA splicing machinery. Silencing of several spliceosome proteins reduced cell viability in a panel of NSCLC cell lines, but not in non-malignant lung fibroblasts and epithelial cells. Interestingly, the cancer-selective lethal target set comprised all seven Sm proteins that, together with small nuclear RNA, form the core structure of most spliceosome subunits. Interfering with Sm protein expression induced apoptosis in NSCLC cells, but not in non-malignant cells. In silico analysis revealed that Sm proteins are frequently upregulated in NSCLC. For several Sm proteins, increased expression showed a positive correlation with disease severity. Together, our results suggest that the Sm proteins represent particularly useful novel targets for selective treatment of NSCLC.

Indexed as

A549 CellsApoptosisCarcinoma, Non-Small-Cell LungCell LineCell Line, TumorEpithelial CellsFibroblastsHigh-Throughput Screening AssaysHumansLung NeoplasmsMembrane ProteinsRNA InterferenceRNA, Small InterferingRNA SplicingSpliceosomesUp-RegulationMembrane ProteinsRNA, Small Interfering

Identifiers

PMID30705407
OpenAlexW2913565581

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.