Evidence map›Paper›PMID 30119690›Full record

ArticleGenome biology2018

Functional CRISPR screen identifies AP1-associated enhancer regulating FOXF1 to modulate oncogene-induced senescence.

Ruiqi Han, Li Li, Alejandro Piñeiro Ugalde, Arieh Tal, Zohar Manber, Eric Pinto Barbera, Veronica Della Chiara, Ran Elkon, Reuven Agami

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

35 citing papers in PubMed, 58 citations in OpenAlex.

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  9. Cellular senescence: Neither irreversible nor reversible.The Journal of experimental medicine · 2024
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  18. Novel Role of Mammalian Cell Senescence-Sustenance of Muscle Larvae ofOxidative medicine and cellular longevity · 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

9 authors at 3 institutions in 2 countries.

Ruiqi HanDivision of Oncogenomics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Li LiDivision of Oncogenomics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Alejandro Piñeiro UgaldeDivision of Oncogenomics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Arieh TalDivision of Oncogenomics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Zohar ManberDepartment of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel.
Eric Pinto BarberaDivision of Oncogenomics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Veronica Della ChiaraDivision of Oncogenomics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Ran ElkonDepartment of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel. ranel@tauex.tau.ac.il.
Reuven AgamiDivision of Oncogenomics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. r.agami@nki.nl.ORCID 0000-0002-2848-2473
The Netherlands Cancer Institute · NLTel Aviv University · ILErasmus MC · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundFunctional characterization of non-coding elements in the human genome is a major genomic challenge and the maturation of genome-editing technologies is revolutionizing our ability to achieve this task. Oncogene-induced senescence, a cellular state of irreversible proliferation arrest that is enforced following excessive oncogenic activity, is a major barrier against cancer transformation; therefore, bypassing oncogene-induced senescence is a critical step in tumorigenesis. Here, we aim at further identification of enhancer elements that are required for the establishment of this state.

resultsWe first apply genome-wide profiling of enhancer-RNAs (eRNAs) to systematically identify enhancers that are activated upon oncogenic stress. DNA motif analysis of these enhancers indicates AP-1 as a major regulator of the transcriptional program induced by oncogene-induced senescence. We thus constructed a CRISPR-Cas9 sgRNA library designed to target senescence-induced enhancers that are putatively regulated by AP-1 and used it in a functional screen. We identify a critical enhancer that we name Enh

conclusionsOur study elucidates a novel cascade mediated by AP-1 and FOXF1 that regulates oncogene-induced senescence and further demonstrates the power of CRISPR-based functional genomic screens in deciphering the function of non-coding regulatory elements in the genome.

Indexed as

Enhancer Elements, GeneticGenetic TestingOncogenesCellular SenescenceCRISPR-Cas SystemsForkhead Transcription FactorsGene Expression ProfilingHEK293 CellsHumansModels, BiologicalTranscription Factor AP-1Forkhead Transcription FactorsFOXF1 protein, humanTranscription Factor AP-1AP1CRISPREnhancersFOSFOXF1Functional screenGene regulationJUNOncogene-induced senescence

Identifiers

PMID30119690
PMCPMC6097335
OpenAlexW2887827989

What OpenQuestion holds

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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.