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Loss of protein phosphatase 6 confers resistance to MAP kinase pathway inhibition in KRAS and BRAF mutant cells via NF-κB activation

GSE200899 Homo sapiens (human) RNA-seq (gene expression) 18 samples Submitted 2024/09/20 Platform GPL18573
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)
Samples
18 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
Protein phosphatase 6 activates NF-κB to confer sensitivity to MAPK pathway inhibitors in KRAS- and BRAF-mutant cancer cellsScience signaling · 2024
Summary (written by the submitters)
To understand the global impact of PPP6C loss on gene expression, we carried out RNA-seq analysis in parental and PPP6C KO SW620 cells under 2D and 3D culture conditions. SW620 WT (sgNT) and PPP6C KO (sgPPP6C#2, sgPPP6C#3) were cultured in normal petri dish (2D culture) or U-bottom plates (3D culture) for 3 days with three independent replicates for each cell sample.
Read the full summary ↓
A total of 4,337 genes were found to be differentially expressed in the KO cells under at least one condition (FDR < 0.05, ≥ 2-fold change). Among these, 1,123 genes were significant up- or down-regulated in PPP6C KO cells under both 2D and 3D conditions. Unsupervised clustering analysis identified three large clusters of gene expression patterns: cluster 1 were upregulated in the PPP6C KO cells primarily under 2D conditions, cluster 2 were upregulated in the PPP6C KO cells under both 2D and 3D conditions, and cluster 3 gene were downregulated genes in the PPP6C KO cells under both 2D and 2D conditions. We next carried out gene set enrichment analysis (GSEA) using the hallmark gene set database to identified pathways that were significantly altered in PPP6C KO cells. Among the pathways upregulated in the PPP6C KO cells under both 2D and 3D conditions, the “TNFA-signaling_via_NFKB” gene set scored as the top one. Both “KRAS_signaling_up” and “PI3K_AKT_mTOR_signaling” gene sets were also significantly upregulated. PPP6C KO has opposite effects on cell proliferation in 2D monolayer vs. 3D tumor spheroid culture. We noticed that 383 genes in the PPP6C KO cells showed opposite changes in 2D vs. 3D conditions. Taken together, gene expression analysis indicates that multiple signaling pathways including the KRAS, PI3K and NF-κB pathways were perturbed in the in PPP6C KO cells and they could contribute to the cell’s decreased sensitivity to MEK inhibitors.
Published in
Protein phosphatase 6 activates NF-κB to confer sensitivity to MAPK pathway inhibitors in KRAS- and BRAF-mutant cancer cells
Zhang H, Read A, Cataisson C et al. · Science signaling 2024 · PMID 38743809 · doi:10.1126/scisignal.add5073
This dataset
Open GSE200899 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 GSE200899_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 PRJNA827158 and SRA study SRP370565. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38743809) ↗
Study design
6 conditions, mostly in triplicate
NT_2D ×3 PP2_2D ×3 PP3_2D ×3 NT_3D ×3 PP2_3D ×3 PP3_3D ×3

Supports a between-group comparison across 18 samples.

How we read this: 6 replicated groups read from 18 sample titles; they account for 18 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
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