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| Item Type: | Article |
|---|---|
| Title: | MYCN and HDAC2 cooperate to repress miR-183 signaling in neuroblastoma |
| Creators Name: | Lodrini, M., Oehme, I., Schroeder, C., Milde, T., Schier, M.C., Kopp-Schneider, A., Schulte, J.H., Fischer, M., De Preter, K., Pattyn, F., Castoldi, M., Muckenthaler, M.U., Kulozik, A.E., Westermann, F., Witt, O. and Deubzer, H.E. |
| Abstract: | MYCN is a master regulator controlling many processes necessary for tumor cell survival. Here, we unravel a microRNA network that causes tumor suppressive effects in MYCN-amplified neuroblastoma cells. In profiling studies, histone deacetylase (HDAC) inhibitor treatment most strongly induced miR-183. Enforced miR-183 expression triggered apoptosis, and inhibited anchorage-independent colony formation in vitro and xenograft growth in mice. Furthermore, the mechanism of miR-183 induction was found to contribute to the cell death phenotype induced by HDAC inhibitors. Experiments to identify the HDAC(s) involved in miR-183 transcriptional regulation showed that HDAC2 depletion induced miR-183. HDAC2 overexpression reduced miR-183 levels and counteracted the induction caused by HDAC2 depletion or HDAC inhibitor treatment. MYCN was found to recruit HDAC2 in the same complexes to the miR-183 promoter, and HDAC2 depletion enhanced promoter-associated histone H4 pan-acetylation, suggesting epigenetic changes preceded transcriptional activation. These data reveal miR-183 tumor suppressive properties in neuroblastoma that are jointly repressed by MYCN and HDAC2, and suggest a novel way to bypass MYCN function. |
| Keywords: | Cell Death, Genetic Promoter Regions, Histone Deacetylase 2, Histone Deacetylase Inhibitors, MicroRNAs, N-Myc Proto-Oncogene Protein, Neuroblastoma, Nuclear Proteins, Oncogene Proteins, Signal Transduction, Tumor Cell Line, Animals, Mice |
| Source: | Nucleic Acids Research |
| ISSN: | 0305-1048 |
| Publisher: | Oxford University Press |
| Volume: | 41 |
| Number: | 12 |
| Page Range: | 6018-6033 |
| Date: | 1 July 2013 |
| Official Publication: | https://doi.org/10.1093/nar/gkt346 |
| PubMed: | View item in PubMed |
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