The MYC/miR-150/MYB/ZDHHC11 network in B-cell lymphoma

The study of this thesis is related to the previously established MYC/miR-150/MYB/ZDHHC11 network regulating Burkitt lymphoma (BL) growth. Our first aim was to study the role of this network in Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL). We found a similar role of three of the network components, while miR-150 overexpression showed no or only very mild effects on HL and DLBCL growth. Therefore, we considered miR-150 as a BL-specific component. Our second aim was to study the specific roles of the protein coding and circular ZDHHC11 gene products. ZDHHC11 belongs to a family of 24 ZDHHC proteins that are characterized by a DHHC motif which mediates palmitoylation. Loss of palmitoylation induced apoptosis in three B-cell lymphoma subtypes indicating the overall importance of protein palmitoylation for B-cell lymphoma. Based on the observed expression patterns we pinpointed seven DHHC family members that might be relevant in B-cell lymphoma. Further studies to elucidate the role of the ZDHHC11 protein were hampered due to difficulties in detecting the protein but provided some evidence that this protein is not a critical factor in regulating BL growth. Lastly, we showed that circular ZDHHC11 RNA transcripts do play a critical role in growth of B cell lymphoma, but this effect is independent of binding miR-150, as deletion of the miR-150 binding site region did not alter the observed phenotype. In summary, we extended current knowledge on the role of the MYC/miR-150/MYB/ZDHHC11 network and addressed the function of ZDHHC11 transcripts and protein in B-cell lymphoma