Dataset Information

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

ABSTRACT: 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.

OTHER RELATED OMICS DATASETS IN: PXD002172PRJNA324839PRJNA324835

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Jesper Velgaard Olsen

PROVIDER: MSV000080762 | MassIVE | Wed Mar 29 11:17:00 BST 2017

SECONDARY ACCESSION(S): PXD002172

REPOSITORIES: MassIVE

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

Rasmussen Mads Heilskov MH Lyskjær Iben I Jersie-Christensen Rosa Rakownikow RR Tarpgaard Line Schmidt LS Primdal-Bengtson Bjarke B Nielsen Morten Muhlig MM Pedersen Jakob Skou JS Hansen Tine Plato TP Hansen Flemming F Olsen Jesper Velgaard JV Olsen Jesper Velgaard JV Pfeiffer Per P Ørntoft Torben Falck TF Andersen Claus Lindbjerg CL

Nature communications 20160816

Oxaliplatin resistance in colorectal cancers (CRC) is a major medical problem, and predictive markers are urgently needed. Recently, miR-625-3p was reported as a promising predictive marker. Herein, we show that miR-625-3p functionally induces oxaliplatin resistance in CRC cells, and identify the signalling networks affected by miR-625-3p. We show that the p38 MAPK activator MAP2K6 is a direct target of miR-625-3p, and, accordingly, is downregulated in non-responder patients of oxaliplatin thera ...[more]

PMID: 27526785

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