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Genome stability disrupted by the circRBM39-RPA2 axis represses breast tumorigenesis

GSE289776 Homo sapiens (human) Non-coding RNA profiling 12 samples Submitted 2025/02/22 Platform GPL24676
At a glance

Non-coding RNA profiling · human · 12 samples

What it is
Non-coding RNA profilingLevels of RNAs that do not code for proteins, such as miRNA or lncRNA.
Organism
Homo sapiens (human)
Topic
Breast cancerThis series is part of our curated briefing on it.
Samples
12 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.
Summary (written by the submitters)
Genome instability (GI) is a hallmark of cancer. GI is associated with accumulative DNA damage and tumor-specific defects in DNA repair. Multiple anti-tumor drugs have been developed to promote persistent GI and to drive DNA damage beyond a threshold that tumor cells can survive. However, regulatory roles of circRNAs in GI and DNA damage remain elusive.
Read the full summary ↓
Through circRNA profiling and an siRNA-mediated screen, we have identified a circRNA termed circRBM39, which is significantly decreased in breast cancer (BC) and disrupts DNA damage response. CircRBM39 inhibits breast tumorigenesis through increasing DNA damage and promoting sensitivity to the anti-tumor drug PARP inhibitor (PARPi). Mechanistically, cytoplasmic circRBM39 interacts with replication protein A2 (RPA2), an essential DNA repair factor, through a 7-nt AG-rich motif and destabilizes RPA2 protein by facilitating HERC2-mediated ubiquitination, thus repressing homologous recombination repair. Importantly, administration of in vitro synthesized circRBM39 substantially inhibits breast tumorigenesis, sensitizes BC cells to PARPi, and renders them susceptible to synthetic lethality (SL) in distinct breast tumorigenesis mouse models. Our findings highlight the interplay between circRNA and GI in cancers, and the SL of circRBM39 to PARPi provides new strategies for RNA-based BC therapeutics.
This dataset
Open GSE289776 in finder → Find more human datasets → Breast cancer 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 GSE289776_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 ↗

Also filed as BioProject PRJNA1224764 and SRA study SRP564377. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Samples in this study

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