2024-03-28T18:01:07Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1358342018-08-13T09:28:50Zcom_10261_112com_10261_1col_10261_365
Insights into epigenetic regulation of microRNA-155 expression in multiple myeloma
Krzemiński, Patryk
Sarasquete, María Eugenia
Misiewicz-Krzeminska, Irena
Corral, Rocío
Corchete, Luis A.
Martín, Ana-África
García-Sanz, Ramón
San Miguel, Jesús F.
Gutiérrez, Norma Carmen
Instituto de Salud Carlos III
Junta de Castilla y León
Grupo Español de Mieloma
Asociación Española Contra el Cáncer
Instituto de Salud Carlos III
Multiple myeloma
LPS
MicroRNA
DNA methylation
[Context]: 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). However, the mechanisms that regulate miR-155 expression in MM are not fully understood. [Objective]: In the present study, we explored the regulation of miRNA-155 in MM by DNA methylation mechanisms and the impact of miR-155 expression in survival of MM patients. [Method]: Primary samples were obtained from 95 patients with newly diagnosed myeloma. Methylation was analyzed by Methylation Specific PCR, sequencing of bisulfite treated DNA and luciferase assay. [Results]: 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). [Conclusion]: This study provides evidence that DNA methylation contributes to miR-155 expression in myeloma cells. Interestingly, the survival data showed an association between miR-155 expression and outcome of MM.
This work was supported by The Fund for Health of Spain (FIS) [PI080568 and PS0901897], the “Gerencia Regional de Salud, Junta de Castilla y León” [GRS 702/A/11] and the Spanish Myeloma Network Program [RD12/0036/0058], “Asociación Española Contra el Cancer” [AECC, GCB120981SAN]. M.E. Sarasquete was supported by Contrato Miguel Servet (CP13/00080).
Peer Reviewed
2016-08-24T10:16:45Z
2016-08-24T10:16:45Z
2015
2016-08-24T10:16:46Z
artículo
http://purl.org/coar/resource_type/c_6501
doi: 10.1016/j.bbagrm.2014.12.002
issn: 0006-3002
Biochimica et Biophysica Acta 1849(3): 353-366 (2015)
http://hdl.handle.net/10261/135834
10.1016/j.bbagrm.2014.12.002
http://dx.doi.org/10.13039/501100004587
http://dx.doi.org/10.13039/501100014180
Sí
none
Elsevier