{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:22:55Z","timestamp":1790662975224,"version":"4.1.0"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T00:00:00Z","timestamp":1645488000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T00:00:00Z","timestamp":1645488000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Backgroud and Aims<\/jats:title>\n            <jats:p>Abnormalities in the tumor protein P53\u00a0(<jats:italic toggle=\"yes\">p53<\/jats:italic>)\u00a0gene and overexpression of mouse double minute 2 homolog (MDM2), a negative regulator of p53, are commonly observed in cancers. p53 destabilization is regulated by endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in cancer. However, the mechanisms remain enigmatic. Canopy homolog 2 (CNPY2) is a key UPR initiator that primarily involved in ER stress and is highly expressed in the liver, but its functional role in regulating liver carcinogenesis is poorly understood. Therefore, we aimed to investigate the role of CNPY2 in hepartocarcinogenesis through URP\u2010dependent p53 destabilization.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>Here, we showed that CNPY2 expression is up\u2010regulated in HCC and negatively correlated with survival rate in liver cancer patients. Deletion of <jats:italic toggle=\"yes\">Cnpy2<\/jats:italic> obliterates diethylnitrosamine (DEN)\u2010induced HCC in mice. Mechanistic studies demonstrated that CNPY2 binds and prevents ribosome proteins from inhibiting MDM2 and enhances the UPR activity of protein kinase RNA\u2010like endoplasmic reticulum kinase and inositol\u2010requiring transmembrane kinase endoribonuclease\u20101\u03b1, leading to p53 destabilization and cell\u2010cycle progression. In addition, transcriptome analyses uncovered that CNPY2 is also required for DEN\u2010induced expression of oncogenes, including c\u2010Jun and fibroblast growth factor 21. Intratumoral injection of nanoparticle\u2010based CRISPR single\u2010guide RNA\/CRISPR\u2010associated protein 9 mRNA against <jats:italic toggle=\"yes\">Cnpy2<\/jats:italic> has antitumor effects in HCC.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>These findings demonstrate that CNPY2 is crucial for liver oncogenesis through UPR\u2010dependent repression of p53 and activation of oncogenes, providing insights into the design of a therapeutic target for HCC.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32318","type":"journal-article","created":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T00:18:59Z","timestamp":1641428339000},"page":"1587-1601","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":21,"title":["Canopy Homolog 2 contributes to liver oncogenesis by promoting unfolded protein response\u2013dependent destabilization of tumor protein P53"],"prefix":"10.1097","volume":"76","author":[{"given":"Feng","family":"Hong","sequence":"first","affiliation":[{"name":"Pelotonia Institute for Immune\u2010Oncology,The Ohio State University Wexner Medical Center,Columbus,Ohio,USA"},{"name":"The Ohio State University James Comprehensive Cancer Center,The Ohio State University Wexner Medical Center,Columbus,Ohio,USA"},{"name":"Division of Medical Oncology,The Ohio State University Wexner Medical Center,Columbus,Ohio,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching Ying","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology,Medical University of South Carolina,Charleston,South Carolina,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyue","family":"Yan","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics & Pharmacology,College of Pharmacy,The Ohio State University,Columbus,Ohio,43210,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhou","family":"Dong","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics & Pharmacology,College of Pharmacy,The Ohio State University,Columbus,Ohio,43210,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuli","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Pelotonia Institute for Immune\u2010Oncology,The Ohio State University Wexner Medical Center,Columbus,Ohio,USA"},{"name":"The Ohio State University James Comprehensive Cancer Center,The Ohio State University Wexner Medical Center,Columbus,Ohio,USA"},{"name":"Division of Medical Oncology,The Ohio State University Wexner Medical Center,Columbus,Ohio,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doyeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Pelotonia Institute for Immune\u2010Oncology,The Ohio State University Wexner Medical Center,Columbus,Ohio,USA"},{"name":"The Ohio State University James Comprehensive Cancer Center,The Ohio State University Wexner Medical Center,Columbus,Ohio,USA"},{"name":"Division of Medical Oncology,The Ohio State University Wexner Medical Center,Columbus,Ohio,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics,The Ohio State University Wexner Medical Center,Columbus,Ohio,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Hematology,The Ohio State University Wexner Medical Center,Columbus,Ohio,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoli","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathology,The Ohio State University Wexner Medical 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