GEO series

DHODH regulates mitochondrial bioenergetics, methylation cycle, and DNA repair in Prostate Adenocarcinoma

GSE305522 Homo sapiens (human) DNA methylation 12 samples Submitted 2026/03/03 Platform GPL16791

At a glance

DNA methylation · human · 12 samples

What it is: DNA methylationChemical marks on DNA that help switch genes on or off.
Organism: Homo sapiens (human)
Topic: Prostate cancerThis series is part of our curated briefing on it.
Samples: 12 samples: 12 samples, each with a distinct title — no replicated groupsGroups 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: DHODH links mitochondrial bioenergetics, one-carbon metabolism, and DNA repair to sustain aggressive prostate adenocarcinomaCell communication and signaling : CCS · 2026

Summary (written by the submitters)

African American (AA) men exhibit disproportionately high incidence rates of prostate cancer (PCa) and a greater propensity for aggressive disease progression. Although epidemiological studies have delineated various risk factors, the precise molecular mechanisms driving the unique tumor biology and clinical disparities in AA men remain poorly characterized.

Read the full summary ↓

Our prior investigations employing in situ analyses of clinical PCa tissues revealed increased uracil incorporation and elevated pyrimidine damage, indicative of heightened DNA repair activity, particularly within AA prostate tumours. Notably, dihydroorotate dehydrogenase (DHODH), a critical enzyme involved in de novo pyrimidine biosynthesis, was significantly overexpressed in PCa, specifically in epithelial cells, with the highest expression observed in patient-derived tumours from AA patients. Through comprehensive gain and loss-of-function experiments across multiple PCa cell lines integrating transcriptomic profiling, DNA methylation sequencing, and metabolomics we demonstrate that DHODH centrally orchestrates mitochondrial bioenergetics, one-carbon metabolism, methylation pathways, and DNA repair mechanisms. Functionally, modulation of DHODH expression directly influenced cellular proliferation, migration, and metastatic potential in vivo, accompanied by alterations in base excision repair (BER)-mediated DNA damage. Collectively, our findings position DHODH as a pivotal metabolic and epigenetic regulator with critical implications for PCa aggressiveness and racial disparities. This work establishes DHODH as a promising therapeutic target, potentially addressing unmet clinical needs and improving outcomes specifically for AA prostate cancer patients.

Published in

DHODH links mitochondrial bioenergetics, one-carbon metabolism, and DNA repair to sustain aggressive prostate adenocarcinoma

Rajaratnam S, Piyarathna DWB, Mehta RK et al. · Cell communication and signaling : CCS 2026 · PMID 41612476 · doi:10.1186/s12964-026-02691-9

This dataset

Open GSE305522 in finder → Find more human RNA-seq datasets → Prostate 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 GSE305522_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: Look for beta-value tables or raw IDAT files among the supplementary files.

Also filed as BioProject PRJNA1306180 and SRA study SRP609015. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41612476) ↗

Study design

12 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 12 sample titles: 12 distinct titles with little repetition. 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

GSM9178725 DHODH_NT_1_1
GSM9178726 DHODH_NT_2_1
GSM9178727 DHODH_NT_3_1
GSM9178728 DHODH_KD1_1_1
GSM9178729 DHODH_KD1_2_1
GSM9178730 DHODH_KD1_3_1
GSM9178731 DHODH_KD2_1_1
GSM9178732 DHODH_KD2_2_1
GSM9178733 DHODH_KD2_3_1
GSM9178734 DHODH_KDR_1_1
GSM9178735 DHODH_KDR_2_1
GSM9178736 DHODH_KDR_3_1

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