GEO series

Targeting metabolic vulnerabilities: REV-ERB agonist SR9009 potentiates sorafenib efficacy in liver cancer

GSE312483 Mus musculus (mouse) RNA-seq (gene expression) 15 samples Submitted 2026/02/11 Platform GPL19057

At a glance

RNA-seq (gene expression) · mouse · 15 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: Mus musculus (mouse)
Samples: 15 samples: 10 distinct titles, 2 of them repeatedGroups 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: Targeting metabolic vulnerabilities: REV-ERB agonist SR9009 potentiates sorafenib efficacy in liver cancerCell death discovery · 2026

Summary (written by the submitters)

Hepatocellular carcinoma (HCC) is one of the most common cancers and the third leading cause of cancer-related death worldwide. The prognosis is poor, with a median survival of 12–15 months in patients with advanced-stage disease. Early diagnosis and the development of new, more effective therapeutic strategies are needed to address the challenges posed by this malignancy.

Read the full summary ↓

Although immune checkpoint inhibitors have replaced multikinase inhibitors as first-line therapy, sorafenib continues to represent a valuable option for patients with contraindications to newer treatments. Based on genome-wide RNA-seq analysis, which identified mitochondrial oxidative phosphorylation (OxPhos) and HMOX1 upregulation as potential pro-survival mechanisms in sorafenib-resistant cells, we investigated whether SR9009, a synthetic agonist of the nuclear receptor REV-ERBα/β, heme competitor, and inhibitor of mitochondrial respiration, could enhance the antitumor efficacy of sorafenib in liver cancer models. Co-treatment with SR9009 and sorafenib significantly enhanced cytotoxic effects in both mouse and human liver cancer cells. This synergistic activity was associated with increased levels of free heme and a complete inhibition of mitochondrial OxPhos. In vivo xenograft studies confirmed that the combination was effective even in sorafenib-resistant tumors. Furthermore, in a N-Nitrosodiethylamine (DEN)-induced HCC model, the combination therapy led to a reduction in size in over 90% of tumor nodules, representing a significant improvement over sorafenib alone. The combination was well tolerated, with no evident signs of acute toxicity. These findings support the concept that the efficacy of anticancer therapies can be enhanced by targeting the metabolic adaptations that tumor cells rely on for survival. Combining sorafenib with agents like SR9009, that disrupt metabolic homeostasis, may offer a promising strategy for treating advanced HCC.

Published in

Targeting metabolic vulnerabilities: REV-ERB agonist SR9009 potentiates sorafenib efficacy in liver cancer

Sabbioni S, Guerriero P, Shankaraiah RC et al. · Cell death discovery 2026 · PMID 41554703 · doi:10.1038/s41420-026-02940-3

This dataset

Open GSE312483 in finder → Find more mouse 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 GSE312483_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 PRJNA1374055 and SRA study SRP651346. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41554703) ↗

Study design

10 distinct titles, 2 of them repeated

H55-RES sorafenib resistant cell-lines, sample ×5 H55.1C wild-type sorafenib sensitive cells, s… ×2

How we read this: Read from 15 sample titles: 10 distinct titles with little repetition. 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

GSM9347148 H55.1C wild-type sorafenib sensitive cells, sample NT1
GSM9347149 H55.1C wild-type sorafenib sensitive cells, sample NT2
GSM9347150 H55-RES sorafenib resistant cell-lines, sample 191
GSM9347151 H55-RES sorafenib resistant cell-lines, sample 412
GSM9347152 H55-RES sorafenib resistant cell-lines, sample 422
GSM9347153 H55-RES sorafenib resistant cell-lines, sample 423
GSM9347154 H55-RES sorafenib resistant cell-lines, sample 424
GSM9347155 H55.1C wild-type cells exposed to sorafenib 2h
GSM9347156 H55.1C wild-type cells exposed to sorafenib 4h
GSM9347157 H55.1C wild-type cells exposed to sorafenib 6h
GSM9347158 H55.1C wild-type cells exposed to sorafenib 8h
GSM9347159 H55.1C wild-type cells exposed to sorafenib 12h
GSM9347160 H55.1C wild-type cells exposed to sorafenib 24h
GSM9347161 H55.1C wild-type cells exposed to sorafenib
GSM9347162 H55.1C wild-type cells exposed to sorafenib + SR9009

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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.