Epigenetic regulation of microRNA expression in Hodgkin lymphoma

Abstract

Epigenetic mechanisms are crucial for the inactivation of key genes related to the survival of Hodgkin lymphoma (HL) cells, and methylation is a frequent epigenetic mechanism of microRNA silencing. We have examined the methylation-induced silencing of tumor suppressor microRNAs in HL cell lines and confirmed our results in patient lymph nodes. In addition, we evaluated the in vitro effectiveness of 5-aza-2-deoxycytidine (5-Aza-dC) in HL cell lines. Ten microRNAs containing CpG islands in their promoter region were re-expressed in both the L-428 and L-1236 cell lines. Interestingly, miR-34a and miR-203, both known tumor suppressor microRNAs, were found to be methylated in cell lines and in patient samples. 5-Aza-dC treatment resulted in a dose-dependent antiproliferative effect at 72 h in all the HL cell lines. In summary, 5-Aza-dC treatment of HL cell lines inhibits proliferation at high doses and produces re-expression of the tumor suppressor microRNAs at low-intermediate doses.

Keywords::

• Lymphoma and Hodgkin disease
• cell lines and animal models
• chemotherapeutic approaches

Acknowledgements

This work was supported by AECC-Catalunya. A.C. is a recipient of a grant from the Universitat de Barcelona (APIF-UB). M.D.B. is a recipient of a Rio Hortega grant (CM13/00205).

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

Supplementary material available online

Supplementary Table I and Figures 1–2 showing further data