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USP10-mediated PFKFB4 deubiquitination induces lung cancer radioresistance by activating the fumarate/Rad51 axis

GSE249850 Homo sapiens (human) RNA-seq (gene expression) 9 samples Submitted 2026/07/15 Platform GPL28038
At a glance

RNA-seq (gene expression) · human · 9 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
Lung cancerThis series is part of our curated briefing on it.
Samples
9 samples: 3 × H1299 cells, Scramble vs 3 × H1299 cells, SiPFKFB4-1 vs 3 × H1299 cells, SiPFKFB4-2Groups 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
PFKFB4 Deubiquitination by USP10 Enhances Fumarate Metabolism to Orchestrate the KDM1A/Rad51 Axis and Confer Radioresistance in Lung CancerAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
Summary (written by the submitters)
Radioresistance is a major cause of radiotherapy failure in lung cancer, and its mechanism has not been fully elucidated. Glucose metabolism is closely related to radioresistance, and targeting key molecules in glucose metabolism is expected to increase radiosensitivity. Our study demonstrated that the expression of the gluconeogenic enzyme PFKFB4 was upregulated in lung cancer.
Read the full summary ↓
Genetic silencing and pharmacological inhibition of PFKFB4 significantly enhanced lung cancer radiosensitivity. Mechanistically, the fumaric acid/Rad51 axis is crucial for PFKFB4-induced radioresistance. PFKFB4 inhibits histone demethylase KDM1A by upregulating fumaric acid, which in turn increases the level of H3K4me1 at the Rad51 promoter region and induces Rad51 transcriptional activation, and ultimately leads to lung cancer radioresistance. Furthermore, by constructing a library of ubiquitinated compounds, the deubiquitinating enzyme USP10 was identified as a key upstream molecule for stabilizing PFKFB4 expression, and USP10 silencing downregulated fumaric acid and Rad51 in a PFKFB4-dependent manner, which in turn increased lung cancer radiosensitivity. In conclusion, the present study reveals that USP10-mediated PFKFB4deubiquitination promotes lung cancer radioresistance through activation of the fumaric acid/Rad51 axis and provides important evidence for the clinical translation of PFKFB4.
Published in
PFKFB4 Deubiquitination by USP10 Enhances Fumarate Metabolism to Orchestrate the KDM1A/Rad51 Axis and Confer Radioresistance in Lung Cancer
Chen Y, Wu Z, Yang Y et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2026 · PMID 42417500 · doi:10.1002/advs.76439
This dataset
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.

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 GSE249850_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1051015 and SRA study SRP477273. Searching any of these in the dataset finder brings you back here.

Study design
3 × H1299 cells, Scramble vs 3 × H1299 cells, SiPFKFB4-1 vs 3 × H1299 cells, SiPFKFB4-2

Supports a between-group comparison across 9 samples.

How we read this: 3 replicated groups read from 9 sample titles; they account for 9 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 Lung cancer datasets

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