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CRISPR-Enabled Profiling of Enhancer RNA-Producing Super-Enhancers in Triple-Negative Breast Cancer Identifies Drivers of Tumor Progression [RNA-Seq]

GSE234324 Homo sapiens (human) RNA-seq (gene expression) 104 samples Submitted 2024/08/14 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 104 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
104 samples: 34 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
CRISPR Screening of Transcribed Super-Enhancers Identifies Drivers of Triple-Negative Breast Cancer ProgressionCancer research · 2024
Summary (written by the submitters)
Triple-negative breast cancer (TNBC) is the most therapeutically recalcitrant form of breast cancer. Pioneering genomic studies have identified the repertoire of expressed genes in the distinct molecular subtypes of breast cancer and have been instrumental in providing diagnostic, prognostic, and therapeutic guidance. Yet breast cancer remains the second leading cause of cancer mortality in women.
Read the full summary ↓
This is due, in part, to the paucity of targeted therapies for triple-negative breast cancer (TNBC). We posit that a systematic analysis of regulatory elements that extend beyond protein coding genes will lead to novel avenues for therapeutic intervention. To this end, we analyzed the regulatory mechanisms of TNBC-specific transcriptional enhancers together with their non-coding enhancer RNA (eRNA) transcripts. We systematically probed the functions of the top 30 eRNA-producing super-enhancers using a high-throughput CRISPR-interference (dCas9-KRAB) assay coupled to RNA-seq that enabled unbiased detection of target genes genome-wide. Utilizing Hi-C, we constructed 3D chromatin interaction maps to annotate direct target genes for each super-enhancer and highlight their proclivity for genes that portend worse clinical outcomes in TNBC patients. To illustrate the utility of this dataset, we selected a novel super-enhancer controlling the nearby PODXL gene and demonstrate that deletion of the super-enhancer (via Cas9 deletion) or specific degradation of its enhancer RNAs (via Cas13 RNA cleavage) leads to profound effects on target gene expression, cell proliferation, and migration. Furthermore, complete knockout of the PODXL super-enhancer leads to a significant decrease in tumor growth and metastatic potential in mouse xenograft experiments. Collectively, this work examines several fundamental questions about how regulatory information encoded into eRNA-producing super-enhancers drives gene expression networks that underlie the biology of triple-negative breast cancer.
Published in
CRISPR Screening of Transcribed Super-Enhancers Identifies Drivers of Triple-Negative Breast Cancer Progression
Lewis MW, King CM, Wisniewska K et al. · Cancer research 2024 · PMID 39186674 · doi:10.1158/0008-5472.CAN-23-3995
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 GSE234324_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 PRJNA980829 and SRA study SRP441416. Searching any of these in the dataset finder brings you back here.

Study design
34 conditions, mostly in triplicate
Positive control CSF1 enhancer ×4 Positive control CSF1 gene promoter ×4 Super-enhancer 39 ×3 Super-enhancer 86 ×3 Super-enhancer 84 ×3 Super-enhancer 32 ×3 Super-enhancer 54 ×3 Super-enhancer 77 ×3 +26 more

Supports a between-group comparison across 104 samples.

How we read this: 34 replicated groups read from 104 sample titles; they account for 104 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

+ 64 more — browse all 104 samples with per-sample file links →

Datasets on a similar topic

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.