Journal
ONCOLOGY REPORTS
Volume 42, Issue 2, Pages 775-784Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2019.7183
Keywords
Burkitt lymphoma; c-MYC; miR-29; methylation; DNMT
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Funding
- INCT for Cancer Control [CNPq 573806/2008-0/FAPERJ E26/170.026/2008]
- FAPERJ [E-26/110.375/2014]
- SWISS-BRIDGE Foundation [1B/2014-2018]
- Brazilian National Cancer Institute (INCA), Health Ministry
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Deregulation of microRNA expression plays a significant role in several cancer types including Burkitt lymphoma (BL). MicroRNA genes may be regulated through epigenetic mechanisms, such as specific histone modifications and/or DNA methylation of CpG islands in promoter regions, or by regions that are located next to microRNA genes. Given the regulatory role of MYC in miR-29 expression, methylation as an additional mechanism for miR-29 silencing was investigated. Methylation of miR-29a/b/c in BL tumour samples and BL cell lines (BL41 and Raji) was assessed by pyrosequencing assay. BL cells were treated with 5-aza-2 '-deoxicitidine (decitabine) and evaluated for miR-29a/b/c expression and methylation status. MYC, DNMT1 and DNMT3B protein expression were accessed by western blotting. For Epstein-Barr virus (EBV) microRNA (miR)-BART6 inhibition, the cells were transiently transfected with anti-BART6-5p. BL tumour samples and BL cell lines presented miR-29a/b1 and miR-29b2/c genes methylated in CpG sites located in both the promoter and enhancer regions. The treatment of BL cells with decitabine reduced methylation, induced miR-29s expression and downregulated MYC protein levels in a dose-dependent manner. Notably, inhibition of EBV miR-BART6-5p combined with decitabine enhanced miR-29 expression in an EBV-BL cell line. In conclusion, the miR-29a/b1 and miR-29b2/c genes have methylated CpG sequences at promoter and enhancer regions that may contribute to the regulation of miR-29 expression in BL tumours. The present findings indicated interplay between MYC and miR-29 regulation, highlighting the potential role of EBV-miRNAs in miR-29 regulation for BL pathogenesis.
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