PXD002172

PXD002172 is an original dataset announced via ProteomeXchange.

Title	miR-625-3p regulates oxaliplatin resistance by targeting MAP2K6-p38 signaling in human colorectal adenocarcinoma cells
Description	Oxaliplatin (oxPt) resistance in colorectal cancers (CRC) is a major unsolved problem. Consequently, predictive markers and a better understanding of resistance mechanisms are urgently needed. To investigate if the recently identified predictive miR-625-3p is functionally involved in oxPt resistance, stable and inducible models of miR-625-3p dysregulation were analyzed. Ectopic expression of miR-625-3p in CRC cells led to increased resistance towards oxPt. The mitogen-activated protein kinase (MAPK) kinase 6 (MAP2K6/MKK6) – an activator of p38 MAPK - was identified as a functional target of miR-625-3p, and, in agreement, was down-regulated in patients not responding to oxPt therapy. The miR-625-3p resistance phenotype could be reversed by anti-miR-625-3p treatment and by ectopic expression of a miR-625-3p insensitive MAP2K6 variant. Transcriptome, proteome and phosphoproteome profiles revealed inactivation of MAP2K6-p38 signaling as a possible driving force behind oxPt resistance. We conclude that miR-625-3p induces oxPt resistance by abrogating MAP2K6-p38 regulated apoptosis and cell cycle control networks. Experimental design for mass spectrometry SILAC experiments can be found at https://figshare.com/s/8e79f008e0e58ec6efc2 or https://doi.org/10.6084/m9.figshare.4888139
HostingRepository	PRIDE
AnnounceDate	2017-04-19
AnnouncementXML	Submission_2019-02-12_07:51:49.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rosa Jersie-Christensen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2015-05-12 08:19:17	ID requested
1	2016-08-12 02:19:56	announced
2	2017-04-19 05:09:10	announced	Updated project metadata.
⏵ 3	2019-02-12 07:51:51	announced	Updated project metadata.

Rasmussen MH, Lyskj, æ, r I, Jersie-Christensen RR, Tarpgaard LS, Primdal-Bengtson B, Nielsen MM, Pedersen JS, Hansen TP, Hansen F, Olsen JV, Pfeiffer P, Ø, rntoft TF, Andersen CL, miR-625-3p regulates oxaliplatin resistance by targeting MAP2K6-p38 signalling in human colorectal adenocarcinoma cells. Nat Commun, 7():12436(2016) [pubmed]

curator keyword: Biomedical

submitter keyword: kf

Jesper Velgaard Olsen
contact affiliation	Univesity of Copenhagen, Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Protein Research, Proteomics Program
contact email	jesper.olsen@cpr.ku.dk
lab head
Rosa Jersie-Christensen
contact affiliation	University of Copenhagen
contact email	rosa.rjc@cpr.ku.dk
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/2016/08/PXD002172

PRIDE project URI

• PRIDE
  1. PXD002172
     1. Label: PRIDE project
     2. Name: miR-625-3p regulates oxaliplatin resistance by targeting MAP2K6-p38 signaling in human colorectal adenocarcinoma cells