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

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.

 Fuente: Haematologica, 2013, 98(4), 640-648

 Editorial: Ferrata Storti Foundation

 Año de publicación: 2013

 Nº de páginas: 9

 Tipo de publicación: Artículo de Revista

 DOI: 10.3324/haematol.2012.070011

 ISSN: 0390-6078,1592-8721

Autoría

MISIEWICZ-KRZEMINSKA, IRENA

SARASQUETE, MARÍA E.

QUWAIDER, DALIA

KRZEMINSKI, PATRYK

TICONA, FANY V.

PAÍNO, TERESA

DELGADO, MANUEL

AIRES, ANDREIA

GARCÍA-SANZ, RAMÓN

SAN MIGUEL, JESÚS F.

GUTIÉRREZ, NORMA C.