Title |
miR-625-3p regulates oxaliplatin resistance by targeting MAP2K6-p38 signalling in human colorectal adenocarcinoma cells
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Published in |
Nature Communications, August 2016
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DOI | 10.1038/ncomms12436 |
Pubmed ID | |
Authors |
Mads Heilskov Rasmussen, Iben Lyskjær, Rosa Rakownikow Jersie-Christensen, Line Schmidt Tarpgaard, Bjarke Primdal-Bengtson, Morten Muhlig Nielsen, Jakob Skou Pedersen, Tine Plato Hansen, Flemming Hansen, Jesper Velgaard Olsen, Per Pfeiffer, Torben Falck Ørntoft, Claus Lindbjerg Andersen |
Abstract |
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 therapy. miR-625-3p-mediated resistance is reversed by anti-miR-625-3p treatment and ectopic expression of a miR-625-3p insensitive MAP2K6 variant. In addition, reduction of p38 signalling by using siRNAs, chemical inhibitors or expression of a dominant-negative MAP2K6 protein induces resistance to oxaliplatin. Transcriptome, proteome and phosphoproteome profiles confirm inactivation of MAP2K6-p38 signalling as one likely mechanism of oxaliplatin resistance. Our study shows that miR-625-3p induces oxaliplatin resistance by abrogating MAP2K6-p38-regulated apoptosis and cell cycle control networks, and corroborates the predictive power of miR-625-3p. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 3 | 100% |
Demographic breakdown
Type | Count | As % |
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Scientists | 1 | 33% |
Science communicators (journalists, bloggers, editors) | 1 | 33% |
Members of the public | 1 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 52 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 14 | 27% |
Researcher | 9 | 17% |
Student > Master | 7 | 13% |
Student > Postgraduate | 4 | 8% |
Student > Bachelor | 4 | 8% |
Other | 4 | 8% |
Unknown | 10 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 19 | 37% |
Agricultural and Biological Sciences | 9 | 17% |
Medicine and Dentistry | 7 | 13% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 2% |
Nursing and Health Professions | 1 | 2% |
Other | 4 | 8% |
Unknown | 11 | 21% |