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| Status |
Public on Jun 09, 2016 |
| Title |
RNA profiling in metastatic colorectal cancer patients treated first-line with oxaliplatin |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Oxaliplatin (oxPt) 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. Here, we have used in vitro models to show that miR-625-3p functionally induces oxPt resistance in CRC cells, and have identified signalling networks affected by miR-625-3p. The p38 MAPK activator MAP2K6 was shown to be a direct target of miR-625-3p, and, accordingly, was downregulated in patients not responding to oxPt therapy. miR-625-3p resistance could be reversed in CRC cells by anti-miR-625-3p treatment and by ectopic expression of a miR-625-3p insensitive MAP2K6 variant. In addition, by reducing p38 MAPK signalling using either siRNA technology, chemical inhibitors to p38 or by ectopic expression of dominant negative MAP2K6 protein we induced resistance to oxPt. Transcriptome, proteome and phosphoproteome profiles revealed inactivation of MAP2K6-p38 signalling as one likely mechanism a possible driving force behind of oxPt resistance. Our study shows that miR-625-3p induces oxPt resistance by abrogating MAP2K6-p38 regulated apoptosis and cell cycle control networks, and corroborates the predictive power of miR-625-3p
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| Overall design |
Cancer and normal epithelium cells were obtained by laser-microdissection from biopsies from first line oxaliplatin treated metastatic colorectal cancer patients.
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| Contributor(s) |
Rasmussen MH, Lyskjær I, Andersen CL |
| Citation(s) |
27526785 |
| |
| Submission date |
Jun 08, 2016 |
| Last update date |
Jul 26, 2018 |
| Contact name |
mads heilskov rasmussen |
| E-mail(s) |
[email protected]
|
| Organization name |
Aarhus University Hospital
|
| Street address |
Brendstrupgårdsvej 21
|
| City |
Aarhus |
| State/province |
Please Select |
| ZIP/Postal code |
8220 |
| Country |
Denmark |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (36)
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| Relations |
| BioProject |
PRJNA324835 |
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