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SRSF7-mediated Alternative Splicing of USO1 Promotes Hepatocellular Carcinoma by Activating the MAPK/ERK1-ELK1 Pathway

GSE262667 Homo sapiens (human) RNA-seq (gene expression) 19 samples Submitted 2024/04/02 Platform GPL21311Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 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
Homo sapiens (human)
Topic
Hepatocellular carcinomaThis series is part of our curated briefing on it.
Samples
19 samples: 6 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.
Summary (written by the submitters)
We conducted a transcriptome-wide survey to identify novel hepatocellular carcinoma (HCC)-associated genes that have undergone aberrant alternative splicing. We revealed that the vesicle transport factor (USO1) is a major alternatively spliced target in HCC, mainly composed of a long wild-type isoform (USO1-L) and a short truncated isoform lacking exons 5 and 15 (USO1-S).
Read the full summary ↓
A markedly increased isoform switching from USO1-L to USO1-S occurs in approximately 80% of HCCs and predicts poor clinical outcomes. USO1-L suppresses HCC cells growth and metastasis through weakening the activation of MAPK/ERK1-ELK1 signaling by interacting with phosphorylated ERK1 and anchoring it onto the Golgi apparatus to reduce its nuclear translocation; while USO1-S confers a loss-of-function effect. The splicing factor SRSF7, which is shown to be hypomethylated and upregulated in HCC, mediates the splicing of USO1-L to produce USO1-S. Notably, the loss of USO1-L in HCC cells induces their resistance to MEK inhibitors; however, restoring USO1-L through antisense oligodeoxynucleotide (ASO)-mediated blockade of switching from USO1-L to USO1-S can reverse this resistance. In summary, our findings highlight the crucial role of aberrantly alternative splicing of USO1 in HCC, as well as the SRSF7-USO1-MAPK axis as a potential target for this malignancy.
This dataset
Open GSE262667 in finder → Find more human RNA-seq datasets → Hepatocellular carcinoma landscape →
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 GSE262667_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 PRJNA1092805 and SRA study SRP498332. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
6 conditions, mostly in triplicate
HeG2, cells, ASO_Ctrl ×3 HeG2, cells, ASO_E5 ×3 HeG2, cells, ASO_E15 ×3 MHCC97H, cells, Flag ×3 MHCC97H, cells, Flag_SRSF7 ×3 HepG2, cells, ASO-E ×2 HepG2, cells, ASO-Ctrl ×1 Tumor ×1

Supports a case/control comparison: 1 samples read as cases, 4 as controls.

How we read this: 6 replicated groups read from 19 sample titles; they account for 17 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
More Hepatocellular carcinoma datasets

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