← BioTransfer GEO Dataset Finder
GEO series

Analysis of MLK3-dependent gene expression in carcinogen-induced murine hepatocellular carcinoma

GSE233074 Mus musculus (mouse) RNA-seq (gene expression) 10 samples Submitted 2024/04/29 Platform GPL19057
At a glance

RNA-seq (gene expression) · mouse · 10 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
10 samples: 3 × DEN-PB treated Wild-type vs 3 × DEN-PB treated MLK3-KO vs 2 × Water Control Wild-type vs 2 × Water Control MLK3-KOGroups 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)
Hepatocellular carcinoma (HCC) is one of the most common gastrointestinal (GI) malignancies and a major cause of death worldwide, with limited therapeutic options. Although Mixed Lineage Kinase 3 (MLK3), a MAPKKK, has emerged as a key regulator of acute liver injury, inflammation, and non-alcoholic steatohepatitis (NASH), its role in HCC remains unclear.
Read the full summary ↓
TCGA databases suggest an elevated expression of MAP3K11 (gene of MLK3) and TMA studies show higher MLK3 activation in human HCCs compared to the normal livers. We demonstrate here that MLK3 kinase activity is upregulated in Diethylnitrosamine/phenobarbital (DEN/PB)-induced HCC, and MLK3 deficiency (MLK3-/-) alleviates HCC progression. Histological and biochemical analyses reveal that MLK3-/- reduces DEN/PB induced cell proliferation in vivo and MLK3 inhibition by si/shRNA or pharmacological inhibitors reduces cell proliferation and colony formation in vitro. Interestingly, MLK3-/- does not impair DEN-induced liver injury phenotypes at the early stage. RNA-sequencing analysis shows that MLK3-/- modulates the gene signature of various biological pathways, including epithelial-mesenchymal transition (EMT), and reduces TGFβ1&2 expressions. HCC cells overexpressing MLK3 promote EMT, and induction of TGFβ, suggesting MLK3 to be an upstream regulator of TGFβ signaling. In addition, MLK3-/- significantly reduces the activated hepatic stellate cell (HSC) signature, which is increased in DEN/PB-Wild-Type livers. Further analysis suggested that MLK3 might promote a paracrine increase in TGFβ expression leading to pSmad2 induction and HSC activation. Our work thus shows that MLK3 promotes HCC proliferation, TGFβ expression, and HSC activation, implying that pharmacological inhibition of MLK3 may have a significant clinical impact on HCC progression.
This dataset
Open GSE233074 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 GSE233074_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 PRJNA974857 and SRA study SRP438842. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
3 × DEN-PB treated Wild-type vs 3 × DEN-PB treated MLK3-KO vs 2 × Water Control Wild-type vs 2 × Water Control MLK3-KO

Supports a case/control comparison: 3 samples read as cases, 4 as controls.

How we read this: 4 replicated groups read from 10 sample titles; they account for 10 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
Datasets on a similar topic

Search all mouse RNA-seq datasets in GEO →

Share this dataset

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.