@article{10902/32232,
year = {2013},
url = {https://hdl.handle.net/10902/32232},
abstract = {MicroRNA 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 P53 mRNA 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.},
organization = {This work was partially supported by the Spanish FIS (PI080568 and PS0901897), the "Gerencia Regional de Salud, Junta de Castilla y León" (GRS202/A08 and GRS 702/A/11), and the Spanish Myeloma Network Program (RD06/0020/0006). MES is supported by the Ministerio de Sanidad y Consumo (CA08/00212).},
publisher = {Ferrata Storti Foundation},
publisher = {Haematologica, 2013, 98(4), 640-648},
title = {Restoration of microRNA-214 expression reduces growth of myeloma cells through positive regulation of P53 and inhibition of DNA replication.},
author = {Misiewicz-Krzeminska, Irena and Sarasquete, María E. and Quwaider, Dalia and Krzeminski, Patryk and Ticona, Fany V. and Paíno, Teresa and Delgado, Manuel and Aires, Andreia and Ocio San Miguel, Enrique María and García-Sanz, Ramón and San Miguel, Jesús F. and Gutiérrez, Norma C.},
}