GEO series

PRMT5 promotes chemoresistance of breast cancer stem cells by regulating DNA repair gene splicing facilitating an enhanced DNA damage response

GSE261017 Homo sapiens (human) RNA-seq (gene expression) 16 samples Submitted 2024/12/19 Platform GPL18573

At a glance

RNA-seq (gene expression) · human · 16 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: Breast cancerThis series is part of our curated briefing on it.
Samples: 16 samples: 6 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: PRMT5-regulated splicing of DNA repair genes drives chemoresistance in breast cancer stem cellsOncogene · 2025

Summary (written by the submitters)

Breast cancer stem cells (BCSCs) are a rare cell population that are responsible for tumour initiation, metastasis, chemoresistance and tumour relapse. Despite this, the mechanism by which BCSCs withstand genotoxic stress is largely unknown. Here, we uncover a pivotal role for the arginine methyltransferase PRMT5 in mediating BCSC chemoresistance by modulation of DNA repair efficiency.

Read the full summary ↓

Notably, PRMT5 inhibitors synergise with cisplatin and radiotherapy, inducing defective DNA repair thereby potentiating BCSC apoptosis. Mechanistically, we demonstrate the crucial function of PRMT5 in ensuring splicing fidelity of DNA damage response genes, particularly those integral to the Fanconi Anaemia and homologous recombination pathways. A comparison of BCSCs and their bulk cell progeny identified shared (ATM, DDX11, EXO1, FAN1, SLX4) and unique (ATR, RAD17, RAD51D, RUVBL1) PRMT5-dependent alternative splicing events. Surprisingly, these events rarely repressed gene expression, suggesting that PRMT5 inhibition predominantly results in nuclear detention of intron-containing transcripts and the production of non-canonical isoforms with compromised protein function. This study thus reveals promising strategies to improve the therapeutic efficacy of PRMT5 inhibitors that promote effective BCSC eradication.

Published in

PRMT5-regulated splicing of DNA repair genes drives chemoresistance in breast cancer stem cells

Gillespie MS, Chiang K, Regan-Mochrie GL et al. · Oncogene 2025 · PMID 39695328 · doi:10.1038/s41388-024-03264-1

This dataset

Open GSE261017 in finder → Find more human RNA-seq datasets → Breast cancer 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 GSE261017_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 PRJNA1084831 and SRA study SRP493707. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39695328) ↗

Study design

6 conditions, mostly in triplicate

MCF7_AR_DMSO ×3 MCF7_AR_GSK ×3 AU565_AR_DMSO ×3 AU565_AR_GSK ×3 MCF7_Bulk_DMSO ×2 MCF7_Bulk_GSK ×2

Supports a between-group comparison across 16 samples.

How we read this: 6 replicated groups read from 16 sample titles; they account for 16 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

GSM8132472 MCF7_AR_DMSO1 MCF7_AR_DMSO
GSM8132473 MCF7_AR_DMSO2 MCF7_AR_DMSO
GSM8132475 MCF7_AR_DMSO3 MCF7_AR_DMSO
GSM8132476 MCF7_AR_GSK1 MCF7_AR_GSK
GSM8132478 MCF7_AR_GSK2 MCF7_AR_GSK
GSM8132479 MCF7_AR_GSK3 MCF7_AR_GSK
GSM8132481 MCF7_Bulk_DMSO1 MCF7_Bulk_DMSO
GSM8132482 MCF7_Bulk_DMSO2 MCF7_Bulk_DMSO
GSM8132484 MCF7_Bulk_GSK1 MCF7_Bulk_GSK
GSM8132485 MCF7_Bulk_GSK2 MCF7_Bulk_GSK
GSM8132487 AU565_AR_DMSO1 AU565_AR_DMSO
GSM8132488 AU565_AR_DMSO2 AU565_AR_DMSO
GSM8132490 AU565_AR_DMSO3 AU565_AR_DMSO
GSM8132491 AU565_AR_GSK1 AU565_AR_GSK
GSM8132493 AU565_AR_GSK2 AU565_AR_GSK
GSM8132494 AU565_AR_GSK3 AU565_AR_GSK

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GSE10886 A Supervised Risk Predictor of Breast Cancer Based on Biological Subtypes 226 samples same disease briefing · shares breast
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GSE264630 A chemical screen identifies PRMT5 as a therapeutic vulnerability for paclitaxel-resistant triple-negative breast cancer 32 samples shares prmt5, breast

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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.