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Genet."],"abstract":"<jats:p>\n                    Hepatoblastoma (HB) is the most common malignant liver tumor among children. To gain insight into the pathobiology of HB, we performed RNA sequence analysis on 5 patient-derived xenograft lines (HB-243, HB-279, HB-282, HB-284, HB-295) and 1 immortalized cell line (HUH6). Using cultured hepatocytes as a control, we found 2,868 genes that were differentially expressed in all of the HB lines on mRNA level. The most upregulated genes were\n                    <jats:italic>ODAM<\/jats:italic>\n                    ,\n                    <jats:italic>TRIM71<\/jats:italic>\n                    , and\n                    <jats:italic>IGDCC3<\/jats:italic>\n                    , and the most downregulated were\n                    <jats:italic>SAA1<\/jats:italic>\n                    ,\n                    <jats:italic>SAA2<\/jats:italic>\n                    , and\n                    <jats:italic>NNMT<\/jats:italic>\n                    . Protein-protein interaction analysis identified ubiquitination as a key pathway dysregulated in HB.\n                    <jats:italic>UBE2C<\/jats:italic>\n                    , encoding an E2 ubiquitin ligase often overexpressed in cancer cells, was markedly upregulated in 5 of the 6 HB cell lines. Validation studies confirmed UBE2C immunostaining in 20 of 25 HB tumor specimens\n                    <jats:italic>versus<\/jats:italic>\n                    1 of 6 normal liver samples. The silencing of\n                    <jats:italic>UBE2C<\/jats:italic>\n                    in two HB cell models resulted in decreased cell viability. RNA sequencing analysis showed alterations in cell cycle regulation after\n                    <jats:italic>UBE2C<\/jats:italic>\n                    knockdown.\n                    <jats:italic>UBE2C<\/jats:italic>\n                    expression in HB correlated with inferior patient survival. We conclude that\n                    <jats:italic>UBE2C<\/jats:italic>\n                    may hold prognostic utility in HB and that the ubiquitin pathway is a potential therapeutic target in this tumor.\n                  <\/jats:p>","DOI":"10.3389\/fgene.2023.1170940","type":"journal-article","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T00:20:14Z","timestamp":1686529214000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["UBE2C expression is elevated in hepatoblastoma and correlates with inferior patient survival"],"prefix":"10.3389","volume":"14","author":[{"given":"Ruth","family":"Nousiainen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Eloranta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noora","family":"Isoaho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Cairo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markku","family":"Heikinheimo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjut","family":"Pihlajoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1007\/S12079-020-00584-1","article-title":"Identification of potential key genes and miRNAs involved in Hepatoblastoma pathogenesis and prognosis","volume":"151","author":"Aghajanzadeh","year":"2020","journal-title":"J. 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