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CDK8 Inhibition Releases the Muscle Differentiation Blockade in Fusion-driven Alveolar Rhabdomyosarcoma [RNA-seq]

GSE300974 Homo sapiens (human) RNA-seq (gene expression) 30 samples Submitted 2026/06/12 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 30 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
Soft tissue sarcomaThis series is part of our curated briefing on it.
Samples
30 samples: 7 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.
Summary (written by the submitters)
Alveolar rhabdomyosarcoma (aRMS) is a fusion-driven pediatric cancer with poor survival and limited therapeutic options. To uncover novel vulnerabilities, we employed complex-based analysis of the functional genomic dataset (Depmap), identifying CDK8 as a novel dependency in aRMS. Both CDK8 knockout or pharmacologic inhibition impaired tumor cell growth and induced myogenic differentiation in vitro and in vivo.
Read the full summary ↓
Compared to genetic loss, CDK8 inhibition induced more dynamic transcriptional changes, suggesting a distinct gain-of-function mechanism of the CDK8 inhibitor. With a genome-scale CRISPR-Cas9 drug modifier screen, we determined that the maximal anti-tumor activity of the CDK8 inhibitor requires the presence of the Mediator kinase module and transcriptional cooperation with the SAGA complex. We further identified SIX4 as a key transcription factor mediating CDK8 inhibitor-induced transcriptional activation of myogenic differentiation genes and tumor cell proliferation. These findings establish a strong rationale for CDK8 inhibition as a differentiation-inducing therapeutic strategy in aRMS.
This dataset
Open GSE300974 in finder → Find more human RNA-seq datasets → Soft tissue sarcoma 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 GSE300974_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 PRJNA1282760 and SRA study SRP594941. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
7 conditions, mostly in triplicate
RNAseq_Rh30_DMSO_D1 ×3 RNAseq_Rh30_DMSO_D7 ×3 RNAseq_Rh30_BI1347_D1 ×3 RNAseq_Rh30_BI1347_D7 ×3 RNAseq_Rh30_sgChr2.2 ×3 RNAseq_Rh30_sgCDK8-3 ×3 RNAseq_Rh30_DMSO_D3 ×2 RNAseq_Rh30_BI1347_D3 ×1 +9 more

Supports a between-group comparison across 20 samples.

How we read this: 7 replicated groups read from 30 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 Soft tissue sarcoma datasets

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.