PXD042498-2

PXD042498 is an original dataset announced via ProteomeXchange.

Title	Total Proteome: Ergolide Mediates Anti-Cancer Effects on Metastatic Uveal Melanoma Cells and Modulates their Cell Lysate and Extracellular Vesicle proteomes.
Description	Uveal melanoma is a poor prognosis cancer with an imperative need for new treatment options. Ergolide, a sesquiterpene lactone isolated from the flowers of Inula species (a medicinal herb), exerts anti-cancer properties. The objective of this study was to 1) evaluate whether ergolide reduced metastatic uveal melanoma (MUM) cell survival/viability in vitro and in vivo; and 2) to understand the molecular mechanism of ergolide action. Ergolide treatment resulted in significant dose-dependent reduction (48.5 to 99.9%; p < 0.0001) in OMM2.5 cell survival in vitro and of normalized primary zebrafish xenograft fluorescence (56%; p< 0.0001) in vivo, compared to vehicle controls. Proteome profiling of ergolide treated OMM2.5 cells, identified 5023 proteins in total with 52 and 55 proteins significantly altered at 4 hours and 24 hours, respectively (p value <0.05; fold-change >1.2). Immunoblot analysis of heme oxygenase 1 (HMOX1), growth/differentiation factor 15 (GDF15) and macrophage migration inhibitory factor (MIF) corroborated the proteomics data. MIF was distinctly downregulated following ergolide treatment. Proteomics of EVs isolated from OMM2.5 cells treated with ergolide detected 2931 total proteins, 2679 of which are recognized as EV proteins based on the Vesiclepedia compendium. 252 additional putative novel EV proteins were also identified. Within the differentially expressed proteins, the proteasomal pathway was primarily altered. Interestingly, BRCA2 and CDKN1A Interacting Protein (BCCIP) and Chitinase Domain Containing 1 (CHID1), were the only proteins significantly differentially expressed by ergolide in both the OMM2.5 cell and EV isolates and they displayed inverse differential expression in the cells versus the EVs. In the TCGA database, no significant correlations occurred between BCCIP and CHID1 transcript levels and overall survival or disease-free survival in UM patients. Ergolide is a novel candidate that shows promise as an anti-proliferative agent for UM/MUM cells. Proteomic profiling of OMM2.5 cell lysates and EVs identified candidate pathways elucidating the action of ergolide and putative biomarkers of UM, that require further examination.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:56:31.989.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kieran Wynne
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-25 07:37:17	ID requested
1	2024-08-26 06:38:07	announced
⏵ 2	2024-10-22 06:56:32	announced	2024-10-22: Updated project metadata.

Sundaramurthi H, Tonelotto V, Wynne K, O'Connell F, O'Reilly E, Costa-Garcia M, Kov, á, csh, á, zi C, Kittel A, Marcone S, Blanco A, Pallinger E, Hambalk, ó S, Piulats Rodriguez JM, Ferdinandy P, O'Sullivan J, Matallanas D, Jensen LD, Giricz Z, Kennedy BN, Ergolide mediates anti-cancer effects on metastatic uveal melanoma cells and modulates their cellular and extracellular vesicle proteomes. Open Res Eur, 3():88(2023) [pubmed]

10.12688/openreseurope.15973.2;

ProteomeXchange project tag: Cancer (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: Melanoma,Erglotide, Q Exactive, Proteomics

Breandán N. Kennedy
contact affiliation	Professor School of Biomolecular and Biomedical Science, University College Dublin, School of Biomolecular and Biomedical Science, Conway Institute Belfield Dublin 4
contact email	brendan.kennedy@ucd.ie
lab head
Kieran Wynne
contact affiliation	University College Dublin
contact email	kieran.wynne1@ucd.ie
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/2024/08/PXD042498

PRIDE project URI

• PRIDE
  1. PXD042498
     1. Label: PRIDE project
     2. Name: Total Proteome: Ergolide Mediates Anti-Cancer Effects on Metastatic Uveal Melanoma Cells and Modulates their Cell Lysate and Extracellular Vesicle proteomes.