GEO series

Liver cancer development driven by the AP-1/c-Jun~Fra2 dimer through c-Myc

GSE261005 Mus musculus (mouse) RNA-seq (gene expression) 19 samples Submitted 2024/04/22 Platform GPL13112

At a glance

RNA-seq (gene expression) · mouse · 19 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: 19 samples: 18 distinct titles, 1 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: Liver cancer development driven by the AP-1/c-Jun~Fra-2 dimer through c-MycProceedings of the National Academy of Sciences of the United States of America · 2024

Summary (written by the submitters)

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. HCC incidence is on the rise, while treatment options remain limited. Thus, a better understanding of the molecular pathways involved in HCC development has become a priority to guide future therapies. While previous studies implicated the AP-1 (Fos/Jun) transcription factor family members c-Fos and c-Jun in HCC formation, the contribution of Fos-related antigens 1 and 2 (Fra-1/2) is unknown.

Read the full summary ↓

Here we show that hepatocyte-restricted expression of a single chain c-Jun~Fra-2 protein, which functionally mimics the c-Jun/Fra-2 AP-1 dimer, results in spontaneous HCC formation in c-Jun~Fra-2hep mice. Several hallmarks of human HCC, such as cell cycle dysregulation and the expression of HCC markers are observed in liver tumors arising in c-Jun~Fra-2hep mice. Tumorigenesis occurs in the context of mild inflammation, low-grade fibrosis and Pparg-driven dyslipidemia. Subsequent analyses revealed increased expression of c-Myc, evidently directly regulated by AP-1 through a conserved distal 3’ enhancer. Importantly, c-Jun~Fra-2-induced tumors revert upon switching off transgene expression, suggesting oncogene addiction to the c-Jun~Fra-2 transgene. Tumors escaping reversion maintained c-Myc and c-Myc target gene expression, likely due to increased c-Fos. Interfering with c-Myc in established tumors using the BET bromodomain inhibitor JQ-1 diminished liver tumor growth in c-Jun~Fra-2 mutant mice. Thus, our data establish c-Jun~Fra-2hep mice as a novel model to study liver tumorigenesis and identify the c-Jun/Fra-2-Myc interaction as a potential target to improve HCC patient stratification and/or therapy.

Published in

Liver cancer development driven by the AP-1/c-Jun~Fra-2 dimer through c-Myc

Bakiri L, Hasenfuss SC, Guío-Carrión A et al. · Proceedings of the National Academy of Sciences of the United States of America 2024 · PMID 38657045 · doi:10.1073/pnas.2404188121

This dataset

Open GSE261005 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 GSE261005_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 PRJNA1084815 and SRA study SRP493681. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38657045) ↗

Study design

18 distinct titles, 1 of them repeated

mutant-1 - 9 months, Tumo ×2

Supports a case/control comparison: 10 samples read as cases, 9 as controls.

How we read this: Read from 19 sample titles: 18 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

GSM8131980 mutant-1 - 2 months
GSM8131981 mutant-2 - 2 months
GSM8131982 mutant-3 - 2 months
GSM8131983 control-1 - 2 months
GSM8131984 control-2 - 2 months
GSM8131985 control-3 - 2 months
GSM8131986 control-4 - 2 months
GSM8131987 control-5 - 2 months
GSM8131988 control-6 - 2 months
GSM8131989 control-1 - 9 months
GSM8131990 control-2 - 9 months
GSM8131991 control-3 - 9 months
GSM8131992 mutant-1 - 9 months, periT
GSM8131993 mutant-2 - 9 months, periT
GSM8131994 mutant-3 - 9 months, periT
GSM8131995 mutant-1 - 9 months, Tumor-1
GSM8131996 mutant-1 - 9 months, Tumor-2
GSM8131997 mutant-2 - 9 months, Tumor
GSM8131998 mutant-3 - 9 months, Tumor

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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.