Evidence map›Paper›PMID 34550356›Full record

ArticleG3 (Bethesda, Md.)2021

A synthetic lethal screen identifies HDAC4 as a potential target in MELK overexpressing cancers.

Lin Zhou, Siqi Zheng, Fernando R Rosas Bringas, Bjorn Bakker, Judith E Simon, Petra L Bakker, Hinke G Kazemier, Michael Schubert, Maurits Roorda, Marcel A T M van Vugt and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in G3 (Bethesda, Md.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.1field-weighted citation impact, top 56% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. 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 1 institution in 1 country.

Lin ZhouEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen 9713 AV, The Netherlands.
Siqi ZhengEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen 9713 AV, The Netherlands.
Fernando R Rosas BringasEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen 9713 AV, The Netherlands.ORCID 0000-0002-7810-0613
Bjorn BakkerEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen 9713 AV, The Netherlands.
Judith E SimonEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen 9713 AV, The Netherlands.
Petra L BakkerEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen 9713 AV, The Netherlands.
Hinke G KazemierEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen 9713 AV, The Netherlands.
Michael SchubertEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen 9713 AV, The Netherlands.
Maurits RoordaDepartment of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen 9713 AV, The Netherlands.ORCID 0000-0001-8779-4680
Marcel A T M van VugtDepartment of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen 9713 AV, The Netherlands.
Michael ChangEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen 9713 AV, The Netherlands.ORCID 0000-0002-1706-3337
Floris FoijerEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen 9713 AV, The Netherlands.ORCID 0000-0003-0989-3127
University Medical Center Groningen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Maternal embryonic leucine zipper kinase (MELK) is frequently overexpressed in cancer, but the role of MELK in cancer is still poorly understood. MELK was shown to have roles in many cancer-associated processes including tumor growth, chemotherapy resistance, and tumor recurrence. To determine whether the frequent overexpression of MELK can be exploited in therapy, we performed a high-throughput screen using a library of Saccharomyces cerevisiae mutants to identify genes whose functions become essential when MELK is overexpressed. We identified two such genes: LAG2 and HDA3. LAG2 encodes an inhibitor of the Skp, Cullin, F-box containing (SCF) ubiquitin-ligase complex, while HDA3 encodes a subunit of the HDA1 histone deacetylase complex. We find that one of these synthetic lethal interactions is conserved in mammalian cells, as inhibition of a human homolog of HDA3 (Histone Deacetylase 4, HDAC4) is synthetically toxic in MELK overexpression cells. Altogether, our work identified a novel potential drug target for tumors that overexpress MELK.

Indexed as

NeoplasmsSaccharomyces cerevisiae ProteinsAnimalsCell Line, TumorCell ProliferationHistone DeacetylasesHumansProtein Serine-Threonine KinasesRepressor ProteinsSaccharomyces cerevisiaeHDA1 protein, S cerevisiaeHDAC4 protein, humanHistone DeacetylasesMELK protein, humanProtein Serine-Threonine KinasesRepressor ProteinsSaccharomyces cerevisiae Proteinscancergenome-wide screenHDAC4MELKsynthetic lethality

Identifiers

PMID34550356
PMCPMC8664443
OpenAlexW3199777956

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.