PXD033400

PXD033400 is an original dataset announced via ProteomeXchange.

Title	Multi omics analysis of adaptation to repeated DNA damage in prostate cancer cells.
Description	DNA damage is frequently utilized as the basis for cancer therapies; however, resistance to DNA damage remains one of the biggest challenges facing cancer patients and their treating clinicians. Critically, the molecular drivers behind resistance are poorly understood. To address this question, we created an isogenic model of prostate cancer exhibiting more aggressive characteristics to better understand the molecular signatures associated with resistance and metastasis. 22Rv1 cells were repeatedly exposed to DNA damage daily for 6 weeks, similar to patient treatment regimes. Using Illumina MethylationEPIC arrays and RNA-seq, we compared the DNA methylation and transcriptional profiles between the parental 22Rv1 cell line and the lineage exposed to prolonged DNA damage. Here we show that repeated DNA damage drives the molecular evolution of cancer cells to a more aggressive phenotype and identify molecular candidates behind this process. Total DNA methylation was increased in cells exposed to repeated DNA damage. Further, RNA-seq demonstrated these cells had dysregulated expression of genes involved in metabolism and the unfolded protein response (UPR) with ASNS identified as central to this process. While limited overlap between RNA-seq and DNA methylation was evident, OGDHL was identified as altered in both data sets. Utilising a second approach we profiled the proteome in 22Rv1 cells following a single dose of radiotherapy. This analysis also highlighted the UPR in response to DNA damage. Together, these analyses identified dysregulation of metabolism and the UPR and identified ASNS and OGDHL as candidate genes for resistance to DNA damage. This work provides critical insight into molecular changes which may underpin treatment resistance and metastasis.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:45:04.689.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Richard Wilson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-23 15:38:50	ID requested
1	2023-04-26 17:51:13	announced
⏵ 2	2023-11-14 08:45:10	announced	2023-11-14: Updated project metadata.

Wang JH, Chuang YF, Chen J, Singh V, Lin FL, Wilson R, Tu L, Ma C, Wong RCB, Wang PY, Zhong J, Hewitt AW, van Wijngaarden P, Dusting GJ, Liu GS, An Integrative Multi-Omics Analysis Reveals MicroRNA-143 as a Potential Therapeutic to Attenuate Retinal Angiogenesis. Nucleic Acid Ther, 32(4):251-266(2022) [pubmed]

submitter keyword: multi-omics, prostate cancer, unfolded protein response,Radiotherapy, DNA damage

Dr Richard Wilson
contact affiliation	Proteomics facility, Central Science Laboratory, University of Tasmania
contact email	richard.wilson@utas.edu.au
lab head
Richard Wilson
contact affiliation	University of Tasmania
contact email	richard.wilson@utas.edu.au
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/04/PXD033400

PRIDE project URI

• PRIDE
  1. PXD033400
     1. Label: PRIDE project
     2. Name: Multi omics analysis of adaptation to repeated DNA damage in prostate cancer cells.