Deregulated miRNAs Contribute to Silencing of B-Cell Specific Transcription Factors and Activation of NF-κB in Classical Hodgkin Lymphoma
A hallmark of classical Hodgkin lymphoma (cHL) is the attenuation of B-cell transcription factors leading to global transcriptional reprogramming. The role of miRNAs (microRNAs) involved in this process is poorly studied. Therefore, we performed global miRNA expression profiling using RNA-seq on com...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-06-01
|
Series: | Cancers |
Subjects: | |
Online Access: | https://www.mdpi.com/2072-6694/13/13/3131 |
id |
doaj-8c4e76945b6c4e6cb59fd24a48e536ea |
---|---|
record_format |
Article |
spelling |
doaj-8c4e76945b6c4e6cb59fd24a48e536ea2021-07-15T15:31:19ZengMDPI AGCancers2072-66942021-06-01133131313110.3390/cancers13133131Deregulated miRNAs Contribute to Silencing of B-Cell Specific Transcription Factors and Activation of NF-κB in Classical Hodgkin LymphomaJulia Paczkowska0Joanna Janiszewska1Adam Ustaszewski2Julia Bein3Marcin Skalski4Agnieszka Dzikiewicz-Krawczyk5Natalia Rozwadowska6Martin-Leo Hansmann7Sylvia Hartmann8Maciej Giefing9Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, PolandInstitute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, PolandInstitute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, PolandDr. Senckenberg Institute of Pathology, Goethe University Frankfurt, D-60590 Frankfurt, GermanyInstitute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, PolandInstitute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, PolandInstitute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, PolandDr. Senckenberg Institute of Pathology, Goethe University Frankfurt, D-60590 Frankfurt, GermanyDr. Senckenberg Institute of Pathology, Goethe University Frankfurt, D-60590 Frankfurt, GermanyInstitute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, PolandA hallmark of classical Hodgkin lymphoma (cHL) is the attenuation of B-cell transcription factors leading to global transcriptional reprogramming. The role of miRNAs (microRNAs) involved in this process is poorly studied. Therefore, we performed global miRNA expression profiling using RNA-seq on commonly used cHL cell lines, non-Hodgkin lymphoma cell lines and sorted normal CD77<sup>+</sup> germinal centre B-cells as controls and characterized the cHL miRNome (microRNome). Among the 298 miRNAs expressed in cHL, 56 were significantly overexpressed and 23 downregulated (<i>p</i> < 0.05) compared to the controls. Moreover, we identified five miRNAs (hsa-miR-9-5p, hsa-miR-24-3p, hsa-miR-196a-5p, hsa-miR-21-5p, hsa-miR-155-5p) as especially important in the pathogenesis of this lymphoma. Target genes of the overexpressed miRNAs in cHL were significantly enriched (<i>p</i> < 0.05) in gene ontologies related to transcription factor activity. Therefore, we further focused on selected interactions with the <i>SPI1</i> and <i>ELF1</i> transcription factors attenuated in cHL and the NF-ĸB inhibitor <i>TNFAIP3</i>. We confirmed the interactions between hsa-miR-27a-5p:SPI1, hsa-miR-330-3p:ELF-1, hsa-miR-450b-5p:ELF-1 and hsa-miR-23a-3p:TNFAIP3, which suggest that overexpression of these miRNAs contributes to silencing of the respective genes. Moreover, by analyzing microdissected HRS cells, we demonstrated that these miRNAs are also overexpressed in primary tumor cells. Therefore, these miRNAs play a role in silencing the B-cell phenotype in cHL.https://www.mdpi.com/2072-6694/13/13/3131classical Hodgkin lymphomamicrodissectionmiRNAloss of B-cell phenotypeNF-κBB-cell transcription factors |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Julia Paczkowska Joanna Janiszewska Adam Ustaszewski Julia Bein Marcin Skalski Agnieszka Dzikiewicz-Krawczyk Natalia Rozwadowska Martin-Leo Hansmann Sylvia Hartmann Maciej Giefing |
spellingShingle |
Julia Paczkowska Joanna Janiszewska Adam Ustaszewski Julia Bein Marcin Skalski Agnieszka Dzikiewicz-Krawczyk Natalia Rozwadowska Martin-Leo Hansmann Sylvia Hartmann Maciej Giefing Deregulated miRNAs Contribute to Silencing of B-Cell Specific Transcription Factors and Activation of NF-κB in Classical Hodgkin Lymphoma Cancers classical Hodgkin lymphoma microdissection miRNA loss of B-cell phenotype NF-κB B-cell transcription factors |
author_facet |
Julia Paczkowska Joanna Janiszewska Adam Ustaszewski Julia Bein Marcin Skalski Agnieszka Dzikiewicz-Krawczyk Natalia Rozwadowska Martin-Leo Hansmann Sylvia Hartmann Maciej Giefing |
author_sort |
Julia Paczkowska |
title |
Deregulated miRNAs Contribute to Silencing of B-Cell Specific Transcription Factors and Activation of NF-κB in Classical Hodgkin Lymphoma |
title_short |
Deregulated miRNAs Contribute to Silencing of B-Cell Specific Transcription Factors and Activation of NF-κB in Classical Hodgkin Lymphoma |
title_full |
Deregulated miRNAs Contribute to Silencing of B-Cell Specific Transcription Factors and Activation of NF-κB in Classical Hodgkin Lymphoma |
title_fullStr |
Deregulated miRNAs Contribute to Silencing of B-Cell Specific Transcription Factors and Activation of NF-κB in Classical Hodgkin Lymphoma |
title_full_unstemmed |
Deregulated miRNAs Contribute to Silencing of B-Cell Specific Transcription Factors and Activation of NF-κB in Classical Hodgkin Lymphoma |
title_sort |
deregulated mirnas contribute to silencing of b-cell specific transcription factors and activation of nf-κb in classical hodgkin lymphoma |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2021-06-01 |
description |
A hallmark of classical Hodgkin lymphoma (cHL) is the attenuation of B-cell transcription factors leading to global transcriptional reprogramming. The role of miRNAs (microRNAs) involved in this process is poorly studied. Therefore, we performed global miRNA expression profiling using RNA-seq on commonly used cHL cell lines, non-Hodgkin lymphoma cell lines and sorted normal CD77<sup>+</sup> germinal centre B-cells as controls and characterized the cHL miRNome (microRNome). Among the 298 miRNAs expressed in cHL, 56 were significantly overexpressed and 23 downregulated (<i>p</i> < 0.05) compared to the controls. Moreover, we identified five miRNAs (hsa-miR-9-5p, hsa-miR-24-3p, hsa-miR-196a-5p, hsa-miR-21-5p, hsa-miR-155-5p) as especially important in the pathogenesis of this lymphoma. Target genes of the overexpressed miRNAs in cHL were significantly enriched (<i>p</i> < 0.05) in gene ontologies related to transcription factor activity. Therefore, we further focused on selected interactions with the <i>SPI1</i> and <i>ELF1</i> transcription factors attenuated in cHL and the NF-ĸB inhibitor <i>TNFAIP3</i>. We confirmed the interactions between hsa-miR-27a-5p:SPI1, hsa-miR-330-3p:ELF-1, hsa-miR-450b-5p:ELF-1 and hsa-miR-23a-3p:TNFAIP3, which suggest that overexpression of these miRNAs contributes to silencing of the respective genes. Moreover, by analyzing microdissected HRS cells, we demonstrated that these miRNAs are also overexpressed in primary tumor cells. Therefore, these miRNAs play a role in silencing the B-cell phenotype in cHL. |
topic |
classical Hodgkin lymphoma microdissection miRNA loss of B-cell phenotype NF-κB B-cell transcription factors |
url |
https://www.mdpi.com/2072-6694/13/13/3131 |
work_keys_str_mv |
AT juliapaczkowska deregulatedmirnascontributetosilencingofbcellspecifictranscriptionfactorsandactivationofnfkbinclassicalhodgkinlymphoma AT joannajaniszewska deregulatedmirnascontributetosilencingofbcellspecifictranscriptionfactorsandactivationofnfkbinclassicalhodgkinlymphoma AT adamustaszewski deregulatedmirnascontributetosilencingofbcellspecifictranscriptionfactorsandactivationofnfkbinclassicalhodgkinlymphoma AT juliabein deregulatedmirnascontributetosilencingofbcellspecifictranscriptionfactorsandactivationofnfkbinclassicalhodgkinlymphoma AT marcinskalski deregulatedmirnascontributetosilencingofbcellspecifictranscriptionfactorsandactivationofnfkbinclassicalhodgkinlymphoma AT agnieszkadzikiewiczkrawczyk deregulatedmirnascontributetosilencingofbcellspecifictranscriptionfactorsandactivationofnfkbinclassicalhodgkinlymphoma AT nataliarozwadowska deregulatedmirnascontributetosilencingofbcellspecifictranscriptionfactorsandactivationofnfkbinclassicalhodgkinlymphoma AT martinleohansmann deregulatedmirnascontributetosilencingofbcellspecifictranscriptionfactorsandactivationofnfkbinclassicalhodgkinlymphoma AT sylviahartmann deregulatedmirnascontributetosilencingofbcellspecifictranscriptionfactorsandactivationofnfkbinclassicalhodgkinlymphoma AT maciejgiefing deregulatedmirnascontributetosilencingofbcellspecifictranscriptionfactorsandactivationofnfkbinclassicalhodgkinlymphoma |
_version_ |
1721299930800193536 |