 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on May 01, 2013 |
| Title |
MYCN and HDAC2 cooperate to repress miR-183 signaling in neuroblastoma. |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
|
| Summary |
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.
|
| |
|
| Overall design |
BE(2)-C neuroblastoma cells were treated with the pan-HDACi HC-toxin (20 nM) or solvent control (methanol) for 24 h in three replicates, respectively.Total RNA was isolated using miRNeasy Mini Kit (Qiagen) according to the manufacturer's instructions. RNA was eluted in water. The quality of total RNA was checked by gel analysis using the total RNA Nanochip assay on an Agilent 2100 Bioanalyzer.
|
| |
|
| Contributor(s) |
Lodrini M, Oehme I, Schroeder C, Milde T, Schier MC, Kopp-Schneider A, Schulte JH, Fischer M, De Preter K, Pattyn F, Castoldi M, Muckenthaler MU, Kulozik AE, Westermann F, Witt O, Deubzer HE |
| Citation(s) |
23625969 |
| |
| Submission date |
Feb 21, 2013 |
| Last update date |
Feb 18, 2019 |
| Contact name |
Marco Lodrini |
| Organization name |
German Cancer Research Center
|
| Street address |
Im Neuenheimer Feld 280
|
| City |
Heidelberg |
| ZIP/Postal code |
69120 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL8179 |
Illumina Human v2 MicroRNA expression beadchip |
|
| Samples (6)
|
|
| Relations |
| BioProject |
PRJNA190034 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE44538_RAW.tar |
70.0 Kb |
(http)(custom) |
TAR |
| GSE44538_non_normalized.txt.gz |
75.8 Kb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...