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Synthetic lethality from the combination of a histone methyltransferase, SUV39H2 inhibitor, and a poly (ADP-ribose) polymerase inhibitor for uterine leiomyosarcoma [RNA-Seq]

GSE297689 Homo sapiens (human) RNA-seq (gene expression) 2 samples Submitted 2025/05/28 Platform GPL21697
At a glance

RNA-seq (gene expression) · human · 2 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
2 samples
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
Synthetic lethality from the combination of a histone methyltransferase SUV39H2 inhibitor and a poly (ADP-ribose) polymerase inhibitor for uterine leiomyosarcomaBMC cancer · 2025
Summary (written by the submitters)
Background: Uterine leiomyosarcoma (uLMS) has a poor prognosis owing to its resistance to chemotherapy. Therefore, novel therapeutic targets for uLMS should be identified. Suppressor license of variegation 3-9 homolog 2 (SUV39H2) is a histone methyltransferase that promotes the repair of double-stranded DNA breaks by recruiting phosphorylated H2AX (γH2AX).
Read the full summary ↓
In this study, we investigated the potential therapeutic targets of SUV39H2 in uLMS and the mechanism of synthetic lethality between PARP inhibitors and the SUV39H2 inhibitor OTS186935. Methods: First, we analyzed the mRNA and protein expression of SUV39H2 in the clinical tissues of uLMS, normal myometrium, and leiomyomas using real-time polymerase chain reaction and immunohistochemistry, respectively. Next, we conducted drug sensitivity assays for OTS186935 alone and in combination with olaparib, a poly (ADP-ribose) polymerase inhibitor, using the uLMS cell lines SK-LMS-1 and SK-UT-1. We performed Western blotting, immunofluorescence, and chromatin immunoprecipitation sequencing (ChIP-seq) to investigate γH2AX following OTS186935 treatment in addition to in vivo experiments using nude mice with subcutaneously implanted uLMS. Results: SUV39H2 expression in uLMS was significantly higher than that in the normal myometrium and leiomyomas. OTS186935 decreased the viability of both cell lines, and its combination with olaparib resulted in synthetic lethality in SK-UT-1 cells (combination index = 0.88). After treatment with OTS186935, γH2AX accumulation decreased. ChIP-seq also showed downregulation of γH2AX following OTS186935 treatment. Notably, the combination of OTS186935 and a PARP inhibitor was significantly more effective in vivo. Conclusion: OTS186935 inhibited double-stranded DNA break repair, as evidenced by γH2AX downregulation by ChIP-seq and other assays. OTS186935 combined with olaparib induces synthetic lethality in patients with uLMS.
Published in
Synthetic lethality from the combination of a histone methyltransferase SUV39H2 inhibitor and a poly (ADP-ribose) polymerase inhibitor for uterine leiomyosarcoma
Toyohara Y, Sone K, Kumegawa K et al. · BMC cancer 2025 · PMID 41402789 · doi:10.1186/s12885-025-15267-6
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 GSE297689_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 PRJNA1265694 and SRA study SRP586614. Searching any of these in the dataset finder brings you back here.

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