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 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.

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Author:Julia PaczkowskaORCiD, Joanna JaniszewskaORCiD, Julia Bein, Markus Schneider, Kinga Bednarek, Adam UstaszewskiORCiD, Sylvia HartmannORCiDGND, Martin-Leo HansmannGND, Maciej GiefingORCiD
URN:urn:nbn:de:hebis:30:3-565454
DOI:https://doi.org/10.3390/cells9102292
ISSN:2073-4409
Parent Title (English):Cells
Publisher:MDPI
Place of publication:Basel
Document Type:Article
Language:English
Date of Publication (online):2020/10/14
Date of first Publication:2020/10/14
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/11/11
Tag:DNA methylation; cHL; epigenetic; microRNA; mir-148a
Volume:9
Issue:2292
Page Number:14
HeBIS-PPN:475949293
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0