Evidence map›Paper›PMID 34267311›Full record

ArticleCommunications biology2021

Three-dimensional CRISPR screening reveals epigenetic interaction with anti-angiogenic therapy.

Michael Y He, Michael M Halford, Ruofei Liu, James P Roy, Zoe L Grant, Leigh Coultas, Niko Thio, Omer Gilan, Yih-Chih Chan, Mark A Dawson and 2 more

Open access · goldAbstract read
In one paragraph

Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 36% 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

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. CRISPR screening in cardiovascular research.Frontiers in cell and developmental biology · 2023
    Review
  5. Review
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

12 authors at 5 institutions in 3 countries.

Michael Y HeTumour Angiogenesis and Microenvironment Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.ORCID 0000-0002-2235-2758
Michael M HalfordTumour Angiogenesis and Microenvironment Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Ruofei LiuTumour Angiogenesis and Microenvironment Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
James P RoyTumour Angiogenesis and Microenvironment Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Zoe L GrantEpigenetics and Development Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
Leigh CoultasEpigenetics and Development Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.ORCID 0000-0001-6466-0890
Niko ThioBioinformatics Core, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Omer GilanSir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia.ORCID 0000-0003-4156-2619
Yih-Chih ChanTranslational Haematology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.ORCID 0000-0003-2177-5406
Mark A DawsonSir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia.ORCID 0000-0002-5464-5029
Marc G AchenTumour Angiogenesis and Microenvironment Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Steven A StackerTumour Angiogenesis and Microenvironment Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. Steven.Stacker@petermac.org.ORCID 0000-0003-4096-9273
The University of Melbourne · AUPeter MacCallum Cancer Centre · AUThe Royal Melbourne Hospital · AUGladstone Institutes · USUniversity Health Network · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Angiogenesis underlies development, physiology and pathogenesis of cancer, eye and cardiovascular diseases. Inhibiting aberrant angiogenesis using anti-angiogenic therapy (AAT) has been successful in the clinical treatment of cancer and eye diseases. However, resistance to AAT inevitably occurs and its molecular basis remains poorly understood. Here, we uncover molecular modifiers of the blood endothelial cell (EC) response to a widely used AAT bevacizumab by performing a pooled genetic screen using three-dimensional microcarrier-based cell culture and CRISPR-Cas9. Functional inhibition of the epigenetic reader BET family of proteins BRD2/3/4 shows unexpected mitigating effects on EC survival and/or proliferation upon VEGFA blockade. Moreover, transcriptomic and pathway analyses reveal an interaction between epigenetic regulation and anti-angiogenesis, which may affect chromosomal structure and activity in ECs via the cell cycle regulator CDC25B phosphatase. Collectively, our findings provide insight into epigenetic regulation of the EC response to VEGFA blockade and may facilitate development of quality biomarkers and strategies for overcoming resistance to AAT.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsEpigenesis, GeneticAngiogenesis InhibitorsBevacizumabBloodEndothelial CellsAngiogenesis InhibitorsBevacizumab

Identifiers

PMID34267311
PMCPMC8282794
OpenAlexW3179482875

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.