The Role of the MYC/miR-150/MYB/ZDHHC11 Network in Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma.

Lotteke J Y M Ziel-Swier,Anke Van Den Berg,Yichen Liu,Fazlyn R Abdul Razak,Rianne Veenstra,Agnieszka Dzikiewicz-Krawczyk,Debora De Jong,Annika Seitz,Bea Rutgers,Jasper Koerts,Joost Kluiver

doi:10.3390/genes13020227

Abstract

We previously described involvement of the MYC/miR-150/MYB/ZDHHC11 network in the growth of Burkitt lymphoma (BL) cells. Here we studied the relevance of this network in the two other B-cell lymphomas: Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL). Expression levels of the network components were assessed at the RNA and protein level. The effect of modulating levels of the network components on cell growth was determined through GFP competition assay. AGO2-RNA immunoprecipitation was performed to validate targeting by miR-150. Expression levels of MYC, MYB and ZDHHC11 were increased, while miR-150 levels were decreased similar to the pattern observed in BL. The knockdown of MYC, MYB and ZDHHC11 decreased the growth of HL and DLBCL cells. In contrast, overexpression of miR-150 did not induce clear phenotypes in HL, and limited the effects in DLBCL. This could not be explained by the differences in overexpression levels. Furthermore, we showed that in HL, ZDHHC11 and MYB are efficiently targeted by miR-150. To conclude, MYC, MYB and ZDHHC11 are critical for the growth of HL and DLBCL cells consistent with the role observed in BL cells, while low endogenous miR-150 levels appeared to be less critical for the growth of HL and DLBCL cells despite the effective targeting of ZDHHC11 and MYB.

Highlights

Publisher’s Note: MDPI stays neutralBurkitt lymphoma (BL) is a highly aggressive germinal center (GC) B-cell derived lymphoma subtype occurring most commonly in children
We already showed similar expression patterns for the network components in Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) as compared to BL, i.e., increased MYB, MYC and ZDHHC11 levels and decreased miR-150 levels compared to GC B-cells [11]
The levels of each of the three distinct ZDHHC11 transcripts were increased in BL, HL and DLBCL cell lines compared to GC B-cells (Figure 1), with significant differences for BL and HL in comparison to GC B-cells

Summary

Introduction

Burkitt lymphoma (BL) is a highly aggressive germinal center (GC) B-cell derived lymphoma subtype occurring most commonly in children. The hallmark of BL is the translocation of the MYC gene locus to one of the immunoglobulin gene loci, which results in high expression of the oncogenic transcription factor MYC [1]. MYC regulates the expression of many protein-coding and non-coding genes [2,3,4,5,6]. One of the non-coding targets is the MYC-repressed microRNA-150 (miR-150), an important tumor suppressor in lymphoma [6,7,8]. Two validated targets of miR-150 in B-cells are the transcription factor. The ZDHHC11 gene encodes a protein that belongs to the zinc finger DHHC domain-containing (ZDHHC) enzyme (S-palmitoyltransferase) family of

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Discussion

Conclusion