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Circadian regulator REV-ERBα is a master regulator of tumor lineage plasticity and an effective therapeutic target [RNA-Seq]

GSE295834 Homo sapiens (human) RNA-seq (gene expression) 18 samples Submitted 2025/10/29 Platform GPL11154
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: 3 × LuCaP35ENZR PDX tumor, Vehicle treated, Day 10, vs 3 × LuCaP35ENZR PDX tumor, SR8278 20 mg/kg, Day 10, vs 3 × LuCaP173.1 PDX tumor, Vehicle treated, Day 10, vs 2 × LuCaP173.1 PDX tumor, SR8278 20 mg/kg, Day 10,Groups 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
Circadian regulator REV-ERBα is a master regulator of tumor lineage plasticity and an effective therapeutic targetProceedings of the National Academy of Sciences of the United States of America · 2025
Summary (written by the submitters)
Epigenetic and transcriptional dysregulation plays a fundamental role in tumor lineage plasticity (LP). However, the underlying mechanisms, especially for the initial events of LP development, are still poorly understood.
Read the full summary ↓
Here, we report that in progression of prostate cancer from adenocarcinoma to treatment-induced neuroendocrine prostate cancer (t-NEPC), anti-AR signaling inhibitors (ARSIs) reprogram the function of a circadian regulator/nuclear receptor REV-ERBα by switching its target gene programs from kinase signaling and metabolic programs to programs of LP, which includes neurogenesis, stem cell and epithelia to mesenchymal transition (EMT) as well as over fifteen LP drivers including POU3F2/BRN2, ASCL1, FOXA2, ONECUT2 and MYCN. Unexpectedly, REV-ERBα facilitates the chromatin occupancy of BRN2, ASCL1 and FOXA1 in their activation of LP programs, thus functioning as a master regulator of ARSI-induced LP driver network. Mechanistically, REV-ERBα induces chromatin accessibility and H3K27ac modification at promoters of LP genes through its recruitment of BRD4 and p300. Overexpression of REV-ERBα alone is sufficient to induce LP and neuroendocrine phenotype and confers cell resistance to ARSI in adenocarcinoma cells. Loss of REV-ERBα potently inhibits NEPC cell growth and abolishes the expression of LP drivers and gene programs. Pharmacological inhibition of REV-ERBα exhibits high potency in blocking the growth of NEPC tumors including patient-derived xenografts. Our findings reveal that therapy-induced LP development entails a coordinated induction of a network of LP drivers and that REV-ERBα is a novel master regulator of the network and a promising therapeutic target for treatment of advanced prostate cancer such as NEPC.
Published in
Circadian regulator REV-ERBα is a master regulator of tumor lineage plasticity and an effective therapeutic target
Zhang X, Yang Y, Zou H et al. · Proceedings of the National Academy of Sciences of the United States of America 2025 · PMID 41231955 · doi:10.1073/pnas.2513468122
This dataset
Open GSE295834 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 GSE295834_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 PRJNA1256460 and SRA study SRP581826. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41231955) ↗
Study design
3 × LuCaP35ENZR PDX tumor, Vehicle treated, Day 10, vs 3 × LuCaP35ENZR PDX tumor, SR8278 20 mg/kg, Day 10, vs 3 × LuCaP173.1 PDX tumor, Vehicle treated, Day 10, vs 2 × LuCaP173.1 PDX tumor, SR8278 20 mg/kg, Day 10,

Supports a case/control comparison: 6 samples read as cases, 1 as controls.

How we read this: 4 replicated groups read from 18 sample titles; they account for 11 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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