TY - JOUR A1 - Paczkowska, Julia A1 - Janiszewska, Joanna A1 - Bein, Julia A1 - Schneider, Markus A1 - Bednarek, Kinga A1 - Ustaszewski, Adam A1 - Hartmann, Sylvia A1 - Hansmann, Martin-Leo A1 - Giefing, Maciej T1 - The tumor suppressive mir-148a is epigenetically inactivated in classical Hodgkin lymphoma T2 - Cells N2 - 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. KW - cHL KW - epigenetic KW - microRNA KW - DNA methylation KW - mir-148a Y1 - 2020 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/56545 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-565454 SN - 2073-4409 VL - 9 IS - 2292 PB - MDPI CY - Basel ER -