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The tumor cells in cHL are referred to as Hodgkin and Reed\u2013Sternberg (HRS) cells. This review provides an overview of the currently known miRNA\u2013target gene interactions. In addition, we pinpointed other potential regulatory roles of microRNAs (miRNAs) by focusing on genes related to processes relevant for cHL pathogenesis, i.e., loss of B-cell phenotypes, immune evasion, and growth support. A cHL-specific miRNA signature was generated based on the available profiling studies. The interactions relevant for cHL were extracted by comprehensively reviewing the existing studies on validated miRNA\u2013target gene interactions. The miRNAs with potential critical roles included miR-155-5p, miR-148a-3p, miR-181a-5p, miR-200, miR-23a-3p, miR-125a\/b, miR-130a-3p, miR-138, and miR-143-3p, which target, amongst others, PU.1, ETS1, HLA-I, PD-L1, and NF-\u03baB component genes. Overall, we provide a comprehensive perspective on the relevant miRNA\u2013target gene interactions which can also serve as a foundation for future functional studies into the specific roles of the selected miRNAs in cHL pathogenesis.<\/jats:p>","DOI":"10.3390\/cancers16061126","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T03:55:34Z","timestamp":1710215734000},"page":"1126","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pinpointing Functionally Relevant miRNAs in Classical Hodgkin Lymphoma Pathogenesis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3370-5600","authenticated-orcid":false,"given":"Yujia","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roza","family":"Cengiz","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7650-2937","authenticated-orcid":false,"given":"Joost","family":"Kluiver","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9239-1050","authenticated-orcid":false,"given":"Arjan","family":"Diepstra","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8894-2638","authenticated-orcid":false,"given":"Anke","family":"Van den Berg","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,12]]},"reference":[{"key":"ref_1","first-page":"1644","article-title":"Typing the histogenetic origin of the tumor cells of lymphocyte-rich classical Hodgkin\u2019s lymphoma in relation to tumor cells of classical and lymphocyte-predominance Hodgkin\u2019s lymphoma","volume":"63","author":"Wacker","year":"2003","journal-title":"Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms","volume":"36","author":"Alaggio","year":"2022","journal-title":"Leukemia"},{"key":"ref_3","first-page":"e2009013","article-title":"EBV in Hodgkin Lymphoma","volume":"1","author":"Massini","year":"2009","journal-title":"Mediterr. 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