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Tumor cell intrinsic dsRNA innate immune response triggered by PARP inhibitor is compromised in BRCA1 deficient breast cancer by repressing IRF3

GSE305504 Homo sapiens (human) RNA-seq (gene expression) 18 samples Submitted 2026/07/15 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 18 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
18 samples
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
Tumor cell intrinsic dsRNA innate immune response triggered by PARP inhibitor is compromised in BRCA1-deficient breast cancer by repressing IRF3Protein & cell · 2026
Summary (written by the submitters)
Poly (ADP-ribose) polymerase 1 (PARP1) inhibition represents promising targeted therapy for BRCA deficient cancer patients based on synthetic lethality theory. Recent evidence shows that efficacy of DNA damage drugs depends on two aspects, DNA repair signaling and immune response. Applying a functional proteomics approach, we find that the function of spliceosome is perturbed by PARP inhibitors via enhancing interaction between PARP1 and SF3B1, a key factor of spliceosome.
Read the full summary ↓
We demonstrate that differential alternative spliced mRNA and accumulation of double strand RNA (dsRNA) are induced by perturbation of spliceosome upon PARP inhibitors treatment, resulting in triggering dsRNA antiviral mimicry innate immune response. Moreover, we identify a novel function of BRCA1, through which BRCA1 regulates innate immune response leading to compromising of the innate immune signaling by downregulation of IRF3 in BRCA1 deficient breast cancer cells, which reduces the sensitivity to PARP inhibitors and causes intrinsic resistance. Polyinosinic-polycytidylic acid (poly(I:C)) is a dsRNA synthetic analog sensitizing PARP inhibitors through further triggering dsRNA signaling. Finally, we show that the combination of PARP inhibitors and poly(I:C) enhances antitumor efficiency in vivo. Overall, our study reveals BRCA1 deficiency impedes tumor cell intrinsic innate immune response, inducing intrinsic resistance to PARP inhibitors that can be overcome when poly(I:C) is combined.
Published in
Tumor cell intrinsic dsRNA innate immune response triggered by PARP inhibitor is compromised in BRCA1-deficient breast cancer by repressing IRF3
Zhang C, Zhou JB, Lei JH et al. · Protein & cell 2026 · PMID 41520145 · doi:10.1093/procel/pwaf104
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 GSE305504_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 PRJNA1306114 and SRA study SRP608990. Searching any of these in the dataset finder brings you back here.

Samples in this study

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