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Multi-kinase inhibition of STE20 kinases is neuroprotective against chemotherapy-induced axon degeneration

GSE298389 Homo sapiens (human) RNA-seq (gene expression) 36 samples Submitted 2025/10/17 Platform GPL20301
At a glance

RNA-seq (gene expression) · human · 36 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)
Samples
36 samples: 18 conditions, mostly in duplicateGroups 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)
Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition resulting from the toxic action of cancer therapies on peripheral neurons. CIPN features axon terminal retraction from target organs leading to a myriad of sensory symptoms such as mechanical and thermal insensitivity, tingling, numbness and burning pain. There are currently no preventative or curative treatments, mostly because the mechanisms leading to axon degeneration upon chemotherapy treatment in humans remain largely unknown.
Read the full summary ↓
We developed a model of CIPN suitable for high-throughput screening that involves progressive axon degeneration culminating in the death of human iPSC-derived sensory neurons exposed to paclitaxel. Using this model, we screened a library of 192 kinase inhibitors and identified 19 neuroprotective compounds. The top neuroprotective compounds all inhibited members of the STE20 family of kinases; MAP4K4, MAP4K6, and MAP4K7. Genetic and pharmacological inhibition confirmed that simultaneous, but not individual, inhibition of these three kinases is necessary for protection against paclitaxel-induced axonal toxicity in our model, and also in human primary DRG neurons. Importantly, pharmacological inhibitors specific to the STE20 family of kinases did not prevent paclitaxel-mediated killing of three breast cancer cell lines. Transcriptomic studies revealed that it was inhibition of the JNK-c-Jun pathway that prevented cell death and inhibition of the MAP4K-p38 axis that rescued axon degeneration. STE20 kinases are, therefore, a potential therapeutic target for mitigating paclitaxel-induced axon degeneration in sensory neurons while maintaining the therapeutic effects of chemotherapy in cancer patients.
This dataset
Open GSE298389 in finder → Find more human RNA-seq datasets →
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 GSE298389_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 PRJNA1269058 and SRA study SRP588319. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
18 conditions, mostly in duplicate
DMSO, biol rep 1, tech ×2 PTX, biol rep 1, tech ×2 GNE-495 + DMSO, biol rep 1, tech ×2 GNE-495 + PTX, biol rep 1, tech ×2 JNK-IN-8 + DMSO, biol rep 1, tech ×2 JNK-IN-8 + PTX, biol rep 1, tech ×2 DMSO, biol rep 2, tech ×2 PTX, biol rep 2, tech ×2 +10 more

Supports a between-group comparison across 36 samples.

How we read this: 18 replicated groups read from 36 sample titles; they account for 36 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
Datasets on a similar topic

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