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

J. Kluiver, Anke van den Berg, Doetje de Jong, T. Blokzijl, G. Harms, E. Bouwman, Susan Jacobs, Sibrand Poppema, Bart-Jan Kroesen

OnderzoeksoutputAcademicpeer review

119 Citaten (Scopus)

Samenvatting

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-kappa B (NF-kappa B) 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-kappa B, 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.

Originele taal-2English
Pagina's (van-tot)3769-3776
Aantal pagina's8
TijdschriftONCOGENE
Volume26
DOI's
StatusPublished - 31-mei-2007

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