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Alternative splicing generates a constitutively active Fn14 isoform that signals independently of TWEAK

GSE335579 Homo sapiens (human) RNA-seq (gene expression) 16 samples Submitted 2026/06/17 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 16 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
16 samples: 4 × Wildtype LX-2 vs 4 × Wildtype LX-2 treated with TWEAK vs 4 × Fn14α Knockout LX-2 vs 4 × Fn14 Knockout LX-2Groups 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)
Fibroblast growth factor-inducible 14 (Fn14) is a tumour necrosis factor (TNF) receptor family member and therapeutic target in cancer and inflammatory disease. However, clinical strategies aimed at blocking its activation by preventing engagement with its ligand TNF-like weak inducer of apoptosis (TWEAK) have demonstrated limited efficacy, suggesting alternative mechanisms of Fn14 activation.
Read the full summary ↓
Here, we identified Fn14β, a novel Fn14 isoform, encoded by the alternatively spliced transcript TNFRSF12A-202. Transcriptomic analyses showed that TNFRSF12A-202 is expressed across human tissues and liver disease contexts, localises to fibrotic regions in vivo, and is associated with reduced overall survival in hepatocellular carcinoma. Structural modelling predicted that Fn14β lacks the extracellular TWEAK-binding domain while retaining the intracellular TRAF-binding signalling domain. CRISPR/Cas9-mediated selective ablation of the canonical Fn14 isoform demonstrated that endogenous Fn14β is expressed and sufficient to drive downstream transcriptional programmes shared with canonical Fn14a. Functional analyses further showed that Fn14β activates NF-κB signalling and promotes proliferation independently of TWEAK. Together, these findings identified Fn14β as a novel constitutively active, TWEAK-independent Fn14 isoform and provided a mechanistic basis for ligand-independent Fn14 signalling, with implications for therapeutic strategies targeting the TWEAK/Fn14 pathway.
This dataset
Open GSE335579 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 GSE335579_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 PRJNA1478922 and SRA study SRP710006. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
4 × Wildtype LX-2 vs 4 × Wildtype LX-2 treated with TWEAK vs 4 × Fn14α Knockout LX-2 vs 4 × Fn14 Knockout LX-2

Supports a case/control comparison: 8 samples read as cases, 4 as controls.

How we read this: 4 replicated groups read from 16 sample titles; they account for 16 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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