GEO series

Menin-RelA complex antagonizes cancer cell-intrinsic and tumour microenvironment-induced NF-κB hyperactivation to suppress pancreatic neuroendocrine tumorigenesis

GSE326578 Homo sapiens (human) RNA-seq (gene expression) 8 samples Submitted 2026/07/11 Platform GPL34284

At a glance

RNA-seq (gene expression) · human · 8 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: 8 samples: 8 samples, each with a distinct title — no replicated groupsGroups 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)

Pancreatic neuroendocrine tumours (PNETs) are rare neuroendocrine cancers with high mortality rates and an immense unmet medical need. While the genetic and immune landscape of PNETs is defined, the molecular mechanisms linking these factors to tumorigenesis remain poorly understood. Here, we identify NF-κB signaling as a key effector pathway that contributes to PNET tumorigenesis, regulated through both cancer cell extrinsic and intrinsic mechanisms.

Read the full summary ↓

CellChat analysis identifies M2-like macrophages as the dominant source of NF-κB-activating cytokines, and co-culture of PNET cancer cells with THP-1-derived M2-macrophages significantly enhances RelA phosphorylation and colony-forming capacity in vitro. Concurrently, we uncovered a cancer cell intrinsic safeguard mechanism wherein the tumour suppressor menin physically associates with RelA to suppress PNET growth in vitro and in vivo. Molecular docking identified key residues mediating the menin-RelA interaction and revealed three clinically relevant menin mutants (P320R, R415P, W423R) that destabilize this complex, compromising menin’s ability to restrain PNET growth. Mechanistically, menin and RelA co-bind κB sites on promoters of proliferation-associated NF-κB target genes, including NR4A1, and epigenetically silence their expression through reduced H3K27ac. Crucially, NR4A1 depletion or small-molecule inhibition suppresses PNET growth in vitro and in vivo. Together, our findings reveal a novel menin-RelA-NR4A1 axis that regulates PNET growth and demonstrates how extrinsic and intrinsic factors converge on NF-κB signaling, highlighting potential therapeutic avenues.

This dataset

Open GSE326578 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 GSE326578_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 PRJNA1445951 and SRA study SRP688181. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

8 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 8 sample titles: 8 distinct titles with little repetition. 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

GSM9634864 T1_z1812
GSM9634865 T2_z2226
GSM9634866 T3_z9608
GSM9634867 T4_z12593
GSM9634868 T5_02000492
GSM9634869 T7_83791081
GSM9634870 T10_z11651
GSM9634871 T11_z5497

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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.