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).
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