Abstract
The role of non-coding RNAs in B-cells lymphoma
In this thesis we explored the role of long non-coding (lnc)RNAs in B cell lymphoma. This very large family of non-coding RNA transcripts are mostly uncharacterized and their role in disease states such as cancer and B cell lymphoma is mainly unknown. The overall aim of this thesis was to characterize expression profiles of normal B cell subsets and to identify and functionally study lncRNAs relevant to the pathogenesis of Burkitt lymphoma and Hodgkin lymphoma, two germinal center B-cell-derived malignancies. The studies described in this thesis showed that lncRNA expression is actively regulated during normal B-cell maturation. In Burkitt lymphoma we showed that knockdown of MYC significantly altered expression of a substantial number of lncRNAs. In Hodgkin lymphoma we showed altered expression of lncRNAs compared to their normal counterparts. For part of the deregulated lncRNAs we have preliminary data to support a regulation in cis. In addition, we observed that a substantial proportion of the lncRNAs interacted with miRNAs, although the overall percentage was lower than the percentage of protein-coding genes interacting with miRNAs. For three lncRNAs we showed a role in growth of B-cell lymphoma cells. No eQTL effects were observed for lncRNAs mapping at Hodgkin lymphoma susceptibility loci, whereas we did find eQTL effects for some of the protein-coding genes at these loci. Together, our data provides comprehensive overviews on the lncRNAs that are expressed and deregulated in normal and malignant B-cells and pinpoints several lncRNAs that contribute to lymphomagenesis.
In this thesis we explored the role of long non-coding (lnc)RNAs in B cell lymphoma. This very large family of non-coding RNA transcripts are mostly uncharacterized and their role in disease states such as cancer and B cell lymphoma is mainly unknown. The overall aim of this thesis was to characterize expression profiles of normal B cell subsets and to identify and functionally study lncRNAs relevant to the pathogenesis of Burkitt lymphoma and Hodgkin lymphoma, two germinal center B-cell-derived malignancies. The studies described in this thesis showed that lncRNA expression is actively regulated during normal B-cell maturation. In Burkitt lymphoma we showed that knockdown of MYC significantly altered expression of a substantial number of lncRNAs. In Hodgkin lymphoma we showed altered expression of lncRNAs compared to their normal counterparts. For part of the deregulated lncRNAs we have preliminary data to support a regulation in cis. In addition, we observed that a substantial proportion of the lncRNAs interacted with miRNAs, although the overall percentage was lower than the percentage of protein-coding genes interacting with miRNAs. For three lncRNAs we showed a role in growth of B-cell lymphoma cells. No eQTL effects were observed for lncRNAs mapping at Hodgkin lymphoma susceptibility loci, whereas we did find eQTL effects for some of the protein-coding genes at these loci. Together, our data provides comprehensive overviews on the lncRNAs that are expressed and deregulated in normal and malignant B-cells and pinpoints several lncRNAs that contribute to lymphomagenesis.
| Original language | English |
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| Qualification | Doctor of Philosophy |
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| Award date | 23-Dec-2016 |
| Place of Publication | [Groningen] |
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| Print ISBNs | 978-90-367-9426-8 |
| Electronic ISBNs | 978-90-367-9425-1 |
| Publication status | Published - 2016 |