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Restoration of microRNA-214 expression reduces growth of myeloma cells through positive regulation of P53 and inhibition of DNA replication

AuthorsMisiewicz-Krzeminska, Irena; Sarasquete, María Eugenia; Krzemiński, Patryk; Paíno, Teresa ; Delgado, Manuel; Ocio, Enrique M. ; García-Sanz, Ramón; San Miguel, Jesús F. ; Gutiérrez, Norma Carmen
Issue Date2013
PublisherFerrata Storti Foundation
CitationHaematologica 98(4): 640-648 (2013)
AbstractMicroRNA have been demonstrated to be deregulated in multiple myeloma. We have previously reported that miR-214 is down-regulated in multiple myeloma compared to in normal plasma cells. The functional role of miR- 214 in myeloma pathogenesis was explored by transfecting myeloma cell lines with synthetic microRNA followed by gene expression profiling. Putative miR-214 targets were validated by luciferase reporter assay. 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 microRNA, gene expression profiling of the 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. miR- 214 directly down-regulated the expression of PSMD10, which encodes the oncoprotein gankyrin, and ASF1B, a histone chaperone required for DNA replication, by binding to their 3'-untranslated regions. In addition, gankyrin inhibition induced an increase of P53mRNA levels and subsequent up-regulation of CDKN1A (p21Waf1/Cip1) and BAX transcripts, which are direct transcriptional targets of p53. In conclusion, MiR-214 functions as a tumor suppressor in myeloma by positive regulation of p53 and inhibition of DNA replication.
DescriptionThis is an open-access paper.-- et al.
Publisher version (URL)http://dx.doi.org/10.3324/haematol.2012.070011
Identifiersdoi: 10.3324/haematol.2012.070011
issn: 0390-6078
e-issn: 1592-8721
Appears in Collections:(IBMCC) Artículos
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