MassIVE MSV000080762

Imported Reanalysis Dataset Public PXD002172

miR-625-3p regulates oxaliplatin resistance by targeting MAP2K6-p38 signaling in human colorectal adenocarcinoma cells

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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. [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: kf

Contact

Principal Investigators:
(in alphabetical order) 		Jesper Velgaard Olsen, Univesity of Copenhagen, Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Protein Research, Proteomics Program, N/A
Submitting User: ccms

Publications

Rasmussen MH, Lyskjær I, Jersie-Christensen RR, Tarpgaard LS, Primdal-Bengtson B, Nielsen MM, Pedersen JS, Hansen TP, Hansen F, Olsen JV, Pfeiffer P, Ørntoft TF, Andersen CL.
miR-625-3p regulates oxaliplatin resistance by targeting MAP2K6-p38 signalling in human colorectal adenocarcinoma cells.
Nat Commun. Epub 2016 Aug 16.

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