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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 28, 2012 |
| Title |
Restoration of miR-214 expression reduces cell growth of myeloma cells through a positive regulation of P53 and inhibition of DNA replication |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
MicroRNAs have been demonstrated to be deregulated in multiple myeloma (MM). We have previously reported the downregulation of miR-214 in MM compared to normal plasma cells. In the present study, we have explored the functional role of miR-214 in myeloma pathogenesis. Ectopic expression of miR-214 reduced cell growth and induced apoptosis of myeloma cells. In order to identify the potential direct target genes of miR-214 which could be involved in the biological pathways regulated by this miRNA, gene expression profiling of H929 myeloma cell line transfected with precursor miR-214 was carried out. Functional analysis revealed significant enrichment for DNA replication, cell cycle phase and DNA binding. We show that miR-214 directly down-regulates the expression of PSMD10, which encodes the oncoprotein gankyrin, and ASF1B, a histone chaperone required for DNA replication, by binding to their 3'-UTR. In addition, gankyrin inhibition induced an increase of P53 mRNA levels and subsequent up-regulation in CDKN1A (p21Waf1/Cip1) and BAX transcripts, which are direct transcriptional targets of p53. In conclusion, we demonstrate that miR-214 function as a tumor suppressor in myeloma by a positive regulation of p53 and inhibition of DNA replication.
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| Overall design |
H929 cell line was transfected with Pre-miR™ miRNA precursors pre-miR-214 or pre-miR™ miRNA negative, non-targeting control#1 (Ambion) at 50 nM concentration, using the nucleofector II system with C-16 program (Amaxa). The experiments were performed in triplicates.
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| Contributor(s) |
Misiewicz-Krzeminska I, Sarasquete ME, Quwaider D, Krzeminski P, Ticona FV, Paino T, Delgado M, Aires A, Ocio EM, Garcia-Sanz R, San Miguel JF, Gutierrez NC |
| Citation(s) |
23100276 |
| Submission date |
Feb 21, 2012 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Norma Carmen Gutierrez |
| E-mail(s) |
normagu@usal.es
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| Phone |
34923291375
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| Organization name |
University Hospital
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| Department |
Hematology
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| Street address |
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| City |
Salamanca |
| ZIP/Postal code |
37007 |
| Country |
Spain |
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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 (6)
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| Relations |
| BioProject |
PRJNA151981 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE35948_RAW.tar |
25.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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