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The Tumor Suppressive mir-148a Is Epigenetically Inactivated in Classical Hodgkin Lymphoma
DNA methylation was shown previously to be a crucial mechanism responsible for transcriptional deregulation in the pathogenesis of classical Hodgkin lymphoma (cHL). To identify epigenetically inactivated miRNAs in cHL, we have analyzed the set of miRNAs downregulated in cHL cell lines using bisulfit...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602210/ https://www.ncbi.nlm.nih.gov/pubmed/33066457 http://dx.doi.org/10.3390/cells9102292 |
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author | Paczkowska, Julia Janiszewska, Joanna Bein, Julia Schneider, Markus Bednarek, Kinga Ustaszewski, Adam Hartmann, Sylvia Hansmann, Martin-Leo Giefing, Maciej |
author_facet | Paczkowska, Julia Janiszewska, Joanna Bein, Julia Schneider, Markus Bednarek, Kinga Ustaszewski, Adam Hartmann, Sylvia Hansmann, Martin-Leo Giefing, Maciej |
author_sort | Paczkowska, Julia |
collection | PubMed |
description | DNA methylation was shown previously to be a crucial mechanism responsible for transcriptional deregulation in the pathogenesis of classical Hodgkin lymphoma (cHL). To identify epigenetically inactivated miRNAs in cHL, we have analyzed the set of miRNAs downregulated in cHL cell lines using bisulfite pyrosequencing. We focused on miRNAs with promoter regions located within or <1000 bp from a CpG island. Most promising candidate miRNAs were further studied in primary Hodgkin and Reed-Sternberg (HRS) cells obtained by laser capture microdissection. Last, to evaluate the function of identified miRNAs, we performed a luciferase reporter assay to confirm miRNA: mRNA interactions and therefore established cHL cell lines with stable overexpression of selected miRNAs for proliferation tests. We found a significant reverse correlation between DNA methylation and expression levels of mir-339-3p, mir-148a-3p, mir-148a-5p and mir-193a-5 demonstrating epigenetic regulation of these miRNAs in cHL cell lines. Moreover, we demonstrated direct interaction between miR-148a-3p and IL15 and HOMER1 transcripts as well as between mir-148a-5p and SUB1 and SERPINH1 transcripts. Furthermore, mir-148a overexpression resulted in reduced cell proliferation in the KM-H2 cell line. In summary, we report that mir-148a is a novel tumor suppressor inactivated in cHL and that epigenetic silencing of miRNAs is a common phenomenon in cHL. |
format | Online Article Text |
id | pubmed-7602210 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76022102020-11-01 The Tumor Suppressive mir-148a Is Epigenetically Inactivated in Classical Hodgkin Lymphoma Paczkowska, Julia Janiszewska, Joanna Bein, Julia Schneider, Markus Bednarek, Kinga Ustaszewski, Adam Hartmann, Sylvia Hansmann, Martin-Leo Giefing, Maciej Cells Article DNA methylation was shown previously to be a crucial mechanism responsible for transcriptional deregulation in the pathogenesis of classical Hodgkin lymphoma (cHL). To identify epigenetically inactivated miRNAs in cHL, we have analyzed the set of miRNAs downregulated in cHL cell lines using bisulfite pyrosequencing. We focused on miRNAs with promoter regions located within or <1000 bp from a CpG island. Most promising candidate miRNAs were further studied in primary Hodgkin and Reed-Sternberg (HRS) cells obtained by laser capture microdissection. Last, to evaluate the function of identified miRNAs, we performed a luciferase reporter assay to confirm miRNA: mRNA interactions and therefore established cHL cell lines with stable overexpression of selected miRNAs for proliferation tests. We found a significant reverse correlation between DNA methylation and expression levels of mir-339-3p, mir-148a-3p, mir-148a-5p and mir-193a-5 demonstrating epigenetic regulation of these miRNAs in cHL cell lines. Moreover, we demonstrated direct interaction between miR-148a-3p and IL15 and HOMER1 transcripts as well as between mir-148a-5p and SUB1 and SERPINH1 transcripts. Furthermore, mir-148a overexpression resulted in reduced cell proliferation in the KM-H2 cell line. In summary, we report that mir-148a is a novel tumor suppressor inactivated in cHL and that epigenetic silencing of miRNAs is a common phenomenon in cHL. MDPI 2020-10-14 /pmc/articles/PMC7602210/ /pubmed/33066457 http://dx.doi.org/10.3390/cells9102292 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Paczkowska, Julia Janiszewska, Joanna Bein, Julia Schneider, Markus Bednarek, Kinga Ustaszewski, Adam Hartmann, Sylvia Hansmann, Martin-Leo Giefing, Maciej The Tumor Suppressive mir-148a Is Epigenetically Inactivated in Classical Hodgkin Lymphoma |
title | The Tumor Suppressive mir-148a Is Epigenetically Inactivated in Classical Hodgkin Lymphoma |
title_full | The Tumor Suppressive mir-148a Is Epigenetically Inactivated in Classical Hodgkin Lymphoma |
title_fullStr | The Tumor Suppressive mir-148a Is Epigenetically Inactivated in Classical Hodgkin Lymphoma |
title_full_unstemmed | The Tumor Suppressive mir-148a Is Epigenetically Inactivated in Classical Hodgkin Lymphoma |
title_short | The Tumor Suppressive mir-148a Is Epigenetically Inactivated in Classical Hodgkin Lymphoma |
title_sort | tumor suppressive mir-148a is epigenetically inactivated in classical hodgkin lymphoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602210/ https://www.ncbi.nlm.nih.gov/pubmed/33066457 http://dx.doi.org/10.3390/cells9102292 |
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