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Interferon regulatory factor 4 mediates non-enzymatic IRE1 dependency in multiple myeloma cells [RNA-Seq]

GSE288674 Homo sapiens (human) RNA-seq (gene expression) 45 samples Submitted 2025/02/04 Platform GPL15433
At a glance

RNA-seq (gene expression) · human · 45 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
Multiple myelomaThis series is part of our curated briefing on it.
Samples
45 samples: 15 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
Interferon regulatory factor 4 mediates nonenzymatic IRE1 dependency in multiple myeloma cellsPLoS biology · 2025
Summary (written by the submitters)
Multiple Myeloma (MM) arises through oncogenic transformation of immunoglobulin-secreting plasma cells. MM often co-opts the central endoplasmic-reticulum (ER)-stress mitigator, inositol-requiring enzyme 1 (IRE1), to sustain malignant growth. While certain MMs require enzymatic IRE1-dependent activation of the transcription factor XBP1s, others display a nonenzymatic IRE1 dependency that is not yet mechanistically understood.
Read the full summary ↓
Here we identify interferon regulatory factor 4 (IRF4), which stimulates genes that promote immune-cell proliferation, as a key conduit for IRE1’s nonenzymatic control of cell-cycle progression in MM. IRE1 silencing increased inhibitory S114/S270 phosphorylation on IRF4, disrupting IRF4’s chromatin-binding and transcriptional activity. IRF4 knockdown recapitulated, whereas IRF4 repletion reversed the anti-proliferative phenotype of IRE1 silencing. Furthermore, phospho-deficient, but not phospho-mimetic, IRF4 mutants rescued proliferation under IRE1 silencing. Functional studies revealed that IRF4 engages the E2F1 and CDC25A genes and promotes CDK2 activation to drive cell-cycle progression. Our results advance mechanistic understanding of IRE1 and IRF4 in MM.
Published in
Interferon regulatory factor 4 mediates nonenzymatic IRE1 dependency in multiple myeloma cells
Oikonomidi I, Kameswaran V, Pham VC et al. · PLoS biology 2025 · PMID 40215234 · doi:10.1371/journal.pbio.3003096
This dataset
Open GSE288674 in finder → Find more human RNA-seq datasets → Multiple myeloma 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 GSE288674_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 PRJNA1219045 and SRA study SRP561423. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40215234) ↗
Study design
15 conditions, mostly in triplicate
AMO-1 shIRF4 Cl. 1 Mock ×3 AMO-1 shIRF4 Cl. 1 8h ×3 AMO-1 shIRF4 Cl. 1 16h ×3 AMO-1 shIRF4 Cl. 1 24h ×3 AMO-1 shIRF4 Cl. 4-3 Mock ×3 AMO-1 shIRF4 Cl. 4-3 8h ×3 AMO-1 shIRF4 Cl. 4-3 16h ×3 AMO-1 shIRF4 Cl. 4-3 24h ×3 +9 more

Supports a between-group comparison across 43 samples.

How we read this: 15 replicated groups read from 45 sample titles; they account for 43 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

+ 5 more — browse all 45 samples with per-sample file links →

More Multiple myeloma datasets

Search all human RNA-seq datasets in GEO →

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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.