MYCN and HDAC2 cooperate to repress miR-183 signaling in neuroblastoma
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...
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| Format: | Online |
| Language: | English |
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Oxford University Press
2013
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695529/ |
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pubmed-3695529 |
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pubmed-36955292013-06-28 MYCN and HDAC2 cooperate to repress miR-183 signaling in neuroblastoma Lodrini, Marco Oehme, Ina Schroeder, Christina Milde, Till Schier, Marie C. Kopp-Schneider, Annette Schulte, Johannes H. Fischer, Matthias De Preter, Katleen Pattyn, Filip Castoldi, Mirco Muckenthaler, Martina U. Kulozik, Andreas E. Westermann, Frank Witt, Olaf Deubzer, Hedwig E. Gene Regulation, Chromatin and Epigenetics 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. Oxford University Press 2013-07 2013-04-26 /pmc/articles/PMC3695529/ /pubmed/23625969 http://dx.doi.org/10.1093/nar/gkt346 Text en © The Author(s) 2013. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Lodrini, Marco Oehme, Ina Schroeder, Christina Milde, Till Schier, Marie C. Kopp-Schneider, Annette Schulte, Johannes H. Fischer, Matthias De Preter, Katleen Pattyn, Filip Castoldi, Mirco Muckenthaler, Martina U. Kulozik, Andreas E. Westermann, Frank Witt, Olaf Deubzer, Hedwig E. |
| spellingShingle |
Lodrini, Marco Oehme, Ina Schroeder, Christina Milde, Till Schier, Marie C. Kopp-Schneider, Annette Schulte, Johannes H. Fischer, Matthias De Preter, Katleen Pattyn, Filip Castoldi, Mirco Muckenthaler, Martina U. Kulozik, Andreas E. Westermann, Frank Witt, Olaf Deubzer, Hedwig E. MYCN and HDAC2 cooperate to repress miR-183 signaling in neuroblastoma |
| author_facet |
Lodrini, Marco Oehme, Ina Schroeder, Christina Milde, Till Schier, Marie C. Kopp-Schneider, Annette Schulte, Johannes H. Fischer, Matthias De Preter, Katleen Pattyn, Filip Castoldi, Mirco Muckenthaler, Martina U. Kulozik, Andreas E. Westermann, Frank Witt, Olaf Deubzer, Hedwig E. |
| author_sort |
Lodrini, Marco |
| title |
MYCN and HDAC2 cooperate to repress miR-183 signaling in neuroblastoma |
| title_short |
MYCN and HDAC2 cooperate to repress miR-183 signaling in neuroblastoma |
| title_full |
MYCN and HDAC2 cooperate to repress miR-183 signaling in neuroblastoma |
| title_fullStr |
MYCN and HDAC2 cooperate to repress miR-183 signaling in neuroblastoma |
| title_full_unstemmed |
MYCN and HDAC2 cooperate to repress miR-183 signaling in neuroblastoma |
| title_sort |
mycn and hdac2 cooperate to repress mir-183 signaling in neuroblastoma |
| description |
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. |
| publisher |
Oxford University Press |
| publishDate |
2013 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695529/ |
| _version_ |
1611990299150647296 |