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TNF-α inhibits the chemotherapy resistance caused by upregulation of the PERK-ATF4 pathway in colorectal cancer cells

GSE281408 Homo sapiens (human) RNA-seq (gene expression) 16 samples Submitted 2024/11/10 Platform GPL16791
At a glance

RNA-seq (gene expression) · human · 16 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
Colorectal cancerThis series is part of our curated briefing on it.
Samples
16 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.
Summary (written by the submitters)
The unfolded protein response (UPR) is a set of important pathways important for maintaining endoplasmic reticulum homeostasis. Recent evidence suggests that the UPR plays an important role in chemo-resistance. However, the underlying mechanisms are not well understood. We previously found that the PERK pathway, one of three branches of the UPR pathway, is crucial for the resistance of colorectal cancer (CRC) cells to 5-fluorouracil.
Read the full summary ↓
In this study, we demonstrated that activating transcription factor 4 (ATF4), the key downstream factor of the PERK pathway, is overexpressed in human CRCs and associated with a poor prognosis. Loss of ATF4 sensitized CRC cells to multiple chemotherapy drugs. RNA-seq analysis revealed that the TNF-α signaling pathway was significantly induced upon chemotherapy drug treatment while repressed by ATF4-knockdown. Addition of TNF-α can further potentiate the cytotoxic effects of chemotherapy drugs to ATF4-knockdown cells, highlighting a potential role of the TNF-α signaling pathway in regulating the ATF4-mediated drug sensitivity modulation. In summary, our findings provide a promising approach to overcoming chemotherapy resistance in colon cancer.
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 GSE281408_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 PRJNA1183815 and SRA study SRP544159. Searching any of these in the dataset finder brings you back here.

Study design
6 conditions, mostly in triplicate
shSc ×3 shSc_5FU24h ×3 shATF4 ×3 shATF4_5FU24h ×3 shSc_5FU48h ×2 shATF4_5FU48h ×2

Supports a between-group comparison across 16 samples.

How we read this: 6 replicated groups read from 16 sample titles; they account for 16 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 Colorectal cancer datasets

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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.