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Regulation of pri-microRNA BIC transcription and processing in Burkitt lymphoma

Oncogene volume 26, pages 3769–3776 (2007)Cite this article

Abstract

BIC is a primary microRNA (pri-miR-155) that can be processed to mature miR-155. In this study, we show the crucial involvement of protein kinase C (PKC) and nuclear factor-κB (NF-κB) in the regulation of BIC expression upon B-cell receptor triggering. Surprisingly, Northern blot analysis did not reveal any miR-155 expression upon induction of BIC expression in the Burkitt lymphoma-derived Ramos cell line, whereas other microRNAs were clearly detectable. Ectopic expression of BIC in Ramos and HEK293 cells resulted in miR-155 expression in HEK293, but not in Ramos cells, suggesting a specific block of BIC to miR-155 processing in Ramos. In line with the results obtained with Ramos, lack of miR-155 expression after induction of BIC expression was also observed in other Burkitt lymphoma cell lines, indicating a generic and specific blockade in the processing of BIC in Burkitt lymphoma. In contrast, induction of BIC expression in normal tonsillar B cells resulted in very high levels of miR-155 expression and induction of BIC expression in Hodgkin's lymphoma cell lines. It also resulted in elevated levels of miR-155. Our data provide evidence for two levels of regulation for mature miR-155 expression: one at the transcriptional level involving PKC and NF-κB, and one at the processing level. Burkitt lymphoma cells not only express low levels of BIC, but also prevent processing of BIC via an, as yet, unknown mechanism.

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Acknowledgements

This study was supported by a grant from the Dutch Cancer Society (RUG 01-2414)

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Authors and Affiliations

  1. Department of Pathology and Laboratory medicine, Section Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    J Kluiver, A van den Berg, D de Jong, T Blokzijl, G Harms, E Bouwman & S Poppema

  2. Department of Pathology and Laboratory Medicine, Section Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    S Jacobs & B-J Kroesen

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  1. J Kluiver
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  2. A van den Berg
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  3. D de Jong
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  7. S Jacobs
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  8. S Poppema
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  9. B-J Kroesen
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Correspondence to B-J Kroesen.

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Kluiver, J., van den Berg, A., de Jong, D. et al. Regulation of pri-microRNA BIC transcription and processing in Burkitt lymphoma. Oncogene 26, 3769–3776 (2007). https://doi.org/10.1038/sj.onc.1210147

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  • DOI: https://doi.org/10.1038/sj.onc.1210147

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