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| Status |
Public on Jun 09, 2016 |
| Title |
Ectopic expression of miR-625-3p in SW620 colorectal cancer cell lines |
| 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 |
Ectopic induction of miR-625-3p or scramble control shRNA were induced by independent treatment with 50 ng/mL doxycycline for 48 hours.
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| Contributor(s) |
Lyskjær I, Rasmussen MH, Andersen CL |
| Citation(s) |
27526785 |
| Submission date |
Jun 08, 2016 |
| Last update date |
Mar 15, 2019 |
| Contact name |
mads heilskov rasmussen |
| E-mail(s) |
mads.heilskov@clin.au.dk
|
| 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) |
| GPL16686 |
[HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA324839 |
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