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Oncoviruses employ various molecular strategies to enhance replication and persistence. Human cytomegalovirus (HCMV), acting as an initiator or promoter, enables immune evasion, supporting tumor growth. HCMV activates pro-oncogenic pathways within infected cells and direct cellular transformation. Thus, HCMV demonstrates characteristics reminiscent of oncoviruses. Cumulative evidence emphasizes the crucial roles of EZH2 and Myc in oncogenesis and stemness. EZH2 and Myc, pivotal regulators of cellular processes, gain significance in the context of oncoviruses and HCMV infections. This axis becomes a central focus for comprehending the mechanisms driving virus-induced oncogenesis. Elevated EZH2 expression is evident in various cancers, making it a prospective target for cancer therapy. On the other hand, Myc, deregulated in over 50% of human cancers, serves as a potent transcription factor governing cellular processes and contributing to tumorigenesis; Myc activates EZH2 expression and induces global gene expression. The Myc\/EZH2 axis plays a critical role in promoting tumor growth in oncoviruses. Considering that HCMV has been shown to manipulate the Myc\/EZH2 axis, there is emerging evidence suggesting that HCMV could be regarded as a potential oncovirus due to its ability to exploit this critical pathway implicated in tumorigenesis.<\/jats:p>","DOI":"10.3390\/cells13060541","type":"journal-article","created":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T05:56:07Z","timestamp":1710914167000},"page":"541","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["EZH2-Myc Hallmark in Oncovirus\/Cytomegalovirus Infections and Cytomegalovirus\u2019 Resemblance to Oncoviruses"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2984-5870","authenticated-orcid":false,"given":"Ranim","family":"El Baba","sequence":"first","affiliation":[{"name":"Department Pathogens & Inflammation-EPILAB EA4266, University of Franche-Comt\u00e9 UFC, 25000 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"Herbein","sequence":"additional","affiliation":[{"name":"Department Pathogens & Inflammation-EPILAB EA4266, University of Franche-Comt\u00e9 UFC, 25000 Besan\u00e7on, France"},{"name":"Department of Virology, CHU Besan\u00e7on, 25030 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-030-57362-1_1","article-title":"An Introduction to Virus Infections and Human Cancer","volume":"217","author":"Schiller","year":"2021","journal-title":"Viruses Hum. 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