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

GSE280973 Homo sapiens (human) RNA-seq (gene expression) 20 samples Submitted 2024/12/01 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 20 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Topic
MedulloblastomaThis series is part of our curated briefing on it.
Samples
20 samples: 8 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Transcriptional regulation of protein synthesis by mediator kinase represents a therapeutic vulnerability in MYC-driven medulloblastomaNature communications · 2025
Summary (written by the submitters)
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.
Read the full summary ↓
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 in vivo and in vivo. Overall, our findings establish a connection between CDK8-mediated transcriptional regulation and mRNA translation, suggesting a promising new therapeutic approach that targets the protein synthesis for MYC-driven MB.
Published in
Transcriptional regulation of protein synthesis by mediator kinase represents a therapeutic vulnerability in MYC-driven medulloblastoma
Wang D, Ritz C, Luo Y et al. · Nature communications 2025 · PMID 41402279 · doi:10.1038/s41467-025-64937-3
This dataset
Open GSE280973 in finder → Find more human RNA-seq datasets → Medulloblastoma landscape →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE280973_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1181569 and SRA study SRP542853. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41402279) ↗
Study design
8 conditions, mostly in triplicate
Medulloblastoma D458 cells, shNull control ×3 Medulloblastoma D458 cells, shRNA knockdown C… ×3 Medulloblastoma D458 cells, CRISPER-Cas9 nega… ×3 Medulloblastoma D458 cells, CRISPER-Cas9 knoc… ×3 Medulloblastoma D425 cells treated with DMSO ×2 Medulloblastoma D425 cells treated with RVU12… ×2 Medulloblastoma D458 cells treated with DMSO ×2 Medulloblastoma D458 cells treated with RVU12… ×2

Supports a case/control comparison: 10 samples read as cases, 6 as controls.

How we read this: 8 replicated groups read from 20 sample titles; they account for 20 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
More Medulloblastoma datasets

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