{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T04:04:37Z","timestamp":1779681877108,"version":"3.53.1"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    We have previously defined the constitutive photomorphogenic\n                    <jats:italic>protein<\/jats:italic>\n                    1 (COP1) gene as a therapeutic target in hepatocellular carcinoma (HCC). A recent study demonstrated that COP1 induces non\u2010alcoholic fatty liver disease (NAFLD), a precursor to HCC, in normal hepatocytes and that reducing COP1 expression significantly improves high\u2010fat diet\u2010induced hepatic steatosis. Thus, in this study, we investigated if the function of COP1 was associated with HCC metabolism and evolution. Silencing of COP1 expression by a target siRNA significantly suppressed long\u2010term colony formation in Huh7, HepG2, Huh1, and PLC\/PRF\/5 HCC cell lines. RNA sequencing of COP1\u2010silenced Huh7 and HepG2 cells revealed the same directional regulation of 24 (14 up\u2010 and 10 down\u2010regulated) genes. Notable molecular alterations were upregulation of AKR1D1 and downregulation of TMEM65, which involves negative regulation of lipid metabolism and promotion of metastasis, respectively. Correlation analysis using GEPIA2 supported inverse relationship between COP1 and AKR1D1 expression and positive relationship between COP1 and TMEM65 expression in HCC clinical samples. Targeting of COP1 reduced fat accumulation and metastatic potential in both HCC parental cells and CD133\n                    <jats:sup>+<\/jats:sup>\n                    liver cancer stem cells. Overexpression of COP1 reversed the phenotypic changes. Collectively, our findings indicate that the COP1 is functionally correlated with HCC lipid metabolism and stemness.\n                  <\/jats:p>","DOI":"10.1111\/gtc.70108","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T12:06:18Z","timestamp":1775477178000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional Role of\n                    <scp>COP1<\/scp>\n                    Gene in Hepatocellular Carcinoma Lipid Metabolism and Stemness"],"prefix":"10.1111","volume":"31","author":[{"given":"Eun\u2010Hye","family":"Jeon","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine Keimyung University School of Medicine  Daegu Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An\u2010Na","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Anatomy Keimyung University School of Medicine  Daegu Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anatomy Keimyung University School of Medicine  Daegu Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keon Uk","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Keimyung University School of Medicine  Daegu Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Mu","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Seoul National University College of Medicine  Seoul Republic of Korea"},{"name":"BK21 FOUR Biomedical Science Project Seoul National University College of Medicine  Seoul Republic of Korea"},{"name":"Medical Research Center Seoul National University College of Medicine  Seoul Republic of Korea"},{"name":"Wide River Institute of Immunology Seoul National University  Hongcheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Ho","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Anatomy Keimyung University School of Medicine  Daegu Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang Seok","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Radiation Biomedical Research Korea Institute of Radiological &amp; Medical Sciences  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0619-5198","authenticated-orcid":false,"given":"In\u2010Chul","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Radiation Biomedical Research Korea Institute of Radiological &amp; Medical Sciences  Seoul Republic of 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