miR‑29 promoter and enhancer methylation identified by pyrosequencing in Burkitt lymhoma cells: Interplay between MYC and miR‑29 regulation

  • Authors:
    • Luciano Mazzoccoli
    • Marcela Cristina Robaina
    • Carlos E. Bacchi
    • Sheila Coelho Soares Lima
    • Claudete Esteves Klumb
  • View Affiliations

  • Published online on: June 3, 2019     https://doi.org/10.3892/or.2019.7183
  • Pages: 775-784
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Abstract

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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August 2019
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Copy and paste a formatted citation
APA
Mazzoccoli, L., Robaina, M.C., Bacchi, C.E., Soares Lima, S.C., & Klumb, C.E. (2019). miR‑29 promoter and enhancer methylation identified by pyrosequencing in Burkitt lymhoma cells: Interplay between MYC and miR‑29 regulation. Oncology Reports, 42, 775-784. https://doi.org/10.3892/or.2019.7183
MLA
Mazzoccoli, L., Robaina, M. C., Bacchi, C. E., Soares Lima, S. C., Klumb, C. E."miR‑29 promoter and enhancer methylation identified by pyrosequencing in Burkitt lymhoma cells: Interplay between MYC and miR‑29 regulation". Oncology Reports 42.2 (2019): 775-784.
Chicago
Mazzoccoli, L., Robaina, M. C., Bacchi, C. E., Soares Lima, S. C., Klumb, C. E."miR‑29 promoter and enhancer methylation identified by pyrosequencing in Burkitt lymhoma cells: Interplay between MYC and miR‑29 regulation". Oncology Reports 42, no. 2 (2019): 775-784. https://doi.org/10.3892/or.2019.7183