Evidence map›Paper›PMID 39574899›Full record

ArticleResearch square2024

Transcriptional Regulation of Protein Synthesis by Mediator Kinase Represents a Therapeutic Vulnerability in MYC-driven Medulloblastoma.

Dong Wang, Caitlin Ritz, Angela Pierce, Bethany Veo, Yuhuan Luo, Breauna Brunt, Nathan Dahl, Ammu Suresh, Natalie Serkova, Sujatha Venkataraman and 5 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Research square, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Dong WangDepartment of Pediatrics, University of Colorado Anschutz Medical Campus; Aurora, CO, USA.
Caitlin RitzDepartment of Pediatrics, University of Colorado Anschutz Medical Campus; Aurora, CO, USA.
Angela PierceDepartment of Pediatrics, University of Colorado Anschutz Medical Campus; Aurora, CO, USA.
Bethany VeoDepartment of Pediatrics, University of Colorado Anschutz Medical Campus; Aurora, CO, USA.
Yuhuan LuoDepartment of Surgery, University of Colorado Anschutz Medical Campus; Aurora, CO, USA.
Breauna BruntDepartment of Pediatrics, University of Colorado Anschutz Medical Campus; Aurora, CO, USA.
Nathan DahlDepartment of Pediatrics, University of Colorado Anschutz Medical Campus; Aurora, CO, USA.ORCID https://orcid.org/0000-0003-2555-1741
Ammu SureshDepartment of Pediatrics, University of Colorado Anschutz Medical Campus; Aurora, CO, USA.
Natalie SerkovaDepartment of Radiology, University of Colorado Anschutz Medical Campus; Aurora, CO, USA.
Sujatha VenkataramanDepartment of Pediatrics, University of Colorado Anschutz Medical Campus; Aurora, CO, USA.
Etienne DanisBiostatistics and Bioinformatics Shared Resource, University of Colorado Cancer Center, Aurora; CO, USA.
Kamil KuśRVYU Therapeutics; Krakow, Poland.
Milena MazanRVYU Therapeutics; Krakow, Poland.
Tomasz RzymskiRVYU Therapeutics; Krakow, Poland.
Rajeev VibhakarDepartment of Pediatrics, University of Colorado Anschutz Medical Campus; Aurora, CO, USA.

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
NCI NIH HHS P30 CA046934
6 · The paper itself

Abstract

MYC-driven medulloblastoma (MB) is a highly aggressive cancer type with poor prognosis and limited treatment options. Through CRISPR-Cas9 screening of MB cell lines, we identified the Mediator-associated kinase CDK8 as a critical regulator of MYC-driven MB. Loss of CDK8 substantially reduces MYC expression, induces pronounced transcriptional changes, suppresses monosome assembly, and decreases ribosome biogenesis and protein synthesis, consequently inhibiting MB growth. Mechanistically, CDK8 regulates the occupancy of RNA polymerase II at specific chromatin loci, facilitating an epigenetic alteration that promotes the transcriptional regulation of ribosomal genes. Targeting CDK8 effectively diminishes the stem-like neoplastic cells characterized by hyperactive ribosome biogenesis. Furthermore, we demonstrated that the combined inhibition of CDK8 and mTOR synergizes to optimize therapeutic outcomes

Identifiers

PMID39574899
PMCPMC11581124

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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.