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MY-COMP, an inhibitor of the transcriptional activity of YAP-B-MYB, identifies NEK2 as a novel mediator of YAP oncogenesis in uveal melanoma cells [RNA-seq]

GSE227973 Homo sapiens (human) RNA-seq (gene expression) 21 samples Submitted 2024/03/06 Platform GPL18573
At a glance

RNA-seq (gene expression) · human · 21 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
21 samples: 7 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.
Paper
Inhibition of the YAP-MMB interaction and targeting NEK2 as potential therapeutic strategies for YAP-driven cancersOncogene · 2024
Summary (written by the submitters)
Activation of YAP is frequently observed in cancer and is associated with poor outcomes, making it an attractive target for therapeutic intervention. Previous studies have mainly focused on blocking the interaction of YAP with TEAD transcription factors. Here we took a different approach by interfering with the binding of YAP to the transcription factor B-MYB using MY-COMP, a fragment of B-MYB containing the YAP binding domain fused to a nuclear localization signal.
Read the full summary ↓
We found that expression of MY-COMP inhibited the binding of B-MYB to YAP, resulting in growth defects, nuclear abnormalities and polyploidization in HeLa cells. Additionally, MY-COMP interfered with normal cell cycle progression of YAP-dependent uveal melanoma cells, but its effects were much weaker in YAP-independent cutaneous melanoma cell lines. MY-COMP antagonized the YAP-dependent expression of MMB-regulated cell cycle genes, providing an explanation for the observed phenotypes. We identified NIMA-related kinase (NEK2) as a candidate target downstream of YAP and B-MYB, contributing to the transformation of YAP-dependent uveal tumor cell lines. Overall, our findings suggest that targeting selected YAP-MMB regulated genes such as NEK2 or inhibiting the WW-domains of YAP to suppress YAP-regulated cell cycle genes could provide a novel mechanism to antagonize the pro-tumorigenic functions of YAP.
Published in
Inhibition of the YAP-MMB interaction and targeting NEK2 as potential therapeutic strategies for YAP-driven cancers
Jessen M, Gertzmann D, Liss F et al. · Oncogene 2024 · PMID 38182898 · doi:10.1038/s41388-023-02926-w
This dataset
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.

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 GSE227973_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA947601 and SRA study SRP428755. Searching any of these in the dataset finder brings you back here.

Study design
7 conditions, mostly in triplicate
RNAseq_92_1_siCtrl ×3 RNAseq_92_1_siYAP ×3 RNAseq_92_1_MY_COMP ×3 RNAseq_MCF10A_noDox_noOHT ×3 RNAseq_MCF10A_noDox_withOHT ×3 RNAseq_MCF10A_withDox_noOHT ×3 RNAseq_MCF10A_withDox_withOHT ×3

Supports a between-group comparison across 21 samples.

How we read this: 7 replicated groups read from 21 sample titles; they account for 21 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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