Scientific publications

Insights into epigenetic regulation of microRNA-155 expression in multiple myeloma

Krzeminski P (1), Sarasquete ME (2), Misiewicz-Krzeminska I (3), Corral R (2), Corchete LA (2), Martín AA (2), García-Sanz R (2), San Miguel JF (4), Gutiérrez NC (5).
(1) Servicio de Hematología, Hospital Universitario, IBSAL, IBMCC (USAL-CSIC), Salamanca, Spain.
(2) Servicio de Hematología, Hospital Universitario, IBSAL, IBMCC (USAL-CSIC), Salamanca, Spain.
(3) Servicio de Hematología, Hospital Universitario, IBSAL, IBMCC (USAL-CSIC), Salamanca, Spain; National Health Institute, Warsaw, Poland.
(4) Clínica Universidad de Navarra, Centro de Investigación Médica Aplicada, Pamplona, Navarra, Spain.
(5) Servicio de Hematología, Hospital Universitario, IBSAL, IBMCC (USAL-CSIC), Salamanca, Spain

Magazine: Biochimica et Byophysica Acta

Date: Dec 11, 2014

Haematology and Hameotherapy

ABSTRACT

MiR-155 plays a critical role in the development of B-cell malignancies. Previous studies have shown a deregulation of miR-155 in specific cytogenetic subtypes of multiple myeloma (MM).

In the present study, we explored the regulation of miRNA-155 in MM by DNA methylation mechanisms. qRT-PCR analysis revealed that miR-155 was differentially expressed in MM and its upregulation was associated with longer survival.

DNA methylation of CpG island present in the first exon of miR-155 host gene was associated with its low expression in MM cell lines and patient samples. Our results showed for the first time that in vitro methylation of part of the promoter and first exon abrogated the miR-155 expression.

We further showed that miR-155 expression in MM cell lines was increased by demethylating 5-aza-dC treatment and decreased by RNA-directed DNA methylation.

Additionally, we found that LPS "immunological challenge" was insufficient to induce miR-155 expression in MM cell lines with methylated DNA around transcription start site (TSS). This study provides evidence that DNA methylation contributes to miR-155 expression in myeloma cells.

CITATION  Biochim Biophys Acta. 2014 Dec 11. pii: S1874-9399(14)00296-X. doi: 10.1016/j.bbagrm.2014.12.002

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