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Genome-wide CRISPR Screen Identifies BUB1 Kinase as a Druggable Vulnerability in Malignant Pleural Mesothelioma

GSE292620 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/04/09 Platform GPL34281
At a glance

RNA-seq (gene expression) · human · 12 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
MesotheliomaThis series is part of our curated briefing on it.
Samples
12 samples: 6 conditions, mostly in duplicateGroups 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
Genome-wide CRISPR screen identifies BUB1 kinase as a druggable vulnerability in malignant pleural mesotheliomaCell death & disease · 2025
Summary (written by the submitters)
Malignant pleural mesothelioma (MPM) is a rare yet highly aggressive malignancy with a severe prognosis. Compounded by the lack of effective treatment modalities, MPM remains a formidable health challenge. Therefore, identification of actionable liabilities is critical for advancing precision medicine to combat this lethal disease. Here, we exploit an unbiased genome-wide CRISPR screen, integrating and cross-comparing three MPM cell lines with nonmalignant mesothelial cells, to selectively map the gene targets whose depletion indicates a common dependency in MPM cells.
Read the full summary ↓
This systematic approach unveils a cohort of verifiable genes, among which BUB1, a mitotic checkpoint serine/threonine kinase, emerges as a high-confidence hit in cancer cells. Cellular and molecular studies demonstrate that genetic depletion or pharmacological inhibition of BUB1 profoundly impairs MPM cell survival and growth, while inducing G2/M cell cycle arrest, cellular senescence, and apoptosis, and attenuating functional hallmarks of aggressive cancer cells. Transcriptomic profiling of BUB1-depleted cells discloses differential gene expression signatures congruent with cell fate phenotypes, including the reprogramming of mitotic network genes. Mechanistically, BUB1 is indispensable for the proper localization of essential mitotic regulators MAD1, MAD2, and Shugoshin (SGO1), thereby ensuring the functionality of the spindle assembly checkpoint (SAC). Furthermore, BUB1 ablation leads to cytokinesis failure and multinucleation, a phenotype characterized by the downregulation of CDC20, Cyclin A, and Cyclin B, and a reciprocal upregulation of the cyclin-dependent kinase inhibitor p21. Clinically, MPM tumors exhibit elevated levels of BUB1, and high BUB1 expression is associated with shorter patient survival. Our novel findings accentuate comparative CRISPR screens as a powerful platform to explore tumor cell-selective gene essentiality and propose BUB1 kinase as a potential marker and druggable vulnerability with therapeutic implications for MPM.
Published in
Genome-wide CRISPR screen identifies BUB1 kinase as a druggable vulnerability in malignant pleural mesothelioma
Cakiroglu E, Eris S, Oz O et al. · Cell death & disease 2025 · PMID 40180891 · doi:10.1038/s41419-025-07587-z
This dataset
Open GSE292620 in finder → Find more human RNA-seq datasets → Mesothelioma 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 GSE292620_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 PRJNA1240315 and SRA study SRP572253. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40180891) ↗
Study design
6 conditions, mostly in duplicate
H2052 BUB1 knockout cells, (H2052 BUB1 KO), ×2 H2452 BUB1 knockout cells, (H2452 BUB1 KO), ×2 H28 BUB1 knockout cells, (H28 BUB1 KO), ×2 H2052 Renilla knockout cells, (H2052 Ren KO), ×2 H2452 Renilla knockout cells, (H2452 Ren KO), ×2 H28 Renilla knockout cells, (H28 Ren KO), ×2

Supports a between-group comparison across 12 samples.

How we read this: 6 replicated groups read from 12 sample titles; they account for 12 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 Mesothelioma datasets

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