{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T04:11:57Z","timestamp":1768795917969,"version":"3.49.0"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,1,10]],"date-time":"2021-01-10T00:00:00Z","timestamp":1610236800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81872889"],"award-info":[{"award-number":["81872889"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20181332"],"award-info":[{"award-number":["BK20181332"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Hepatic stellate cells (HSCs) play critical roles in liver fibrosis and hepatocellular carcinoma (HCC). Tribbles homolog 2 (TRIB2) is an oncogene implicated in a variety of cancers, including liver cancer. However, the biological function and regulatory mechanism of TRIB2 in HSCs are poorly understood. In addition, little is known about its role in liver fibrosis progression to HCC. Here, we revealed the clinical significance of TRIB2 in liver fibrosis and HCC development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated TRIB2 promoting liver fibrosis in vitro and in vivo. In mouse model of liver fibrosis and HCC, we measured hepatic fibrosis and HCC level through knockdown TRIB2 with shRNA. In addition, we performed western blotting, real\u2010time quantitative PCR, immunofluorescence and co\u2010immunoprecipitation assay to study TRIB2 function in LX\u20102 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TRIB2 expression was strongly upregulated in human fibrotic liver tissues and HCC tissues. TRIB2 colocalized with \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA) in fibrotic and HCC liver tissues. Knockdown of TRIB2 inhibited HSC activation and liver fibrosis in vitro and in vivo. TRIB2 promoted Yes\u2010associated protein (YAP) stabilization, nuclear localization, and subsequent fibrotic gene expression independent of the MST\u2010LATS phosphorylation cascade in HSCs. TRIB2 interacted with YAP to recruit phosphatase 1A (PP1A), promoting PP1A\u2010mediated YAP dephosphorylation. TRIB2 knockdown potently attenuated the development of fibrosis\u2010associated liver cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>TRIB2 is an attractive target for hepatic fibrosis and fibrosis\u2010associated liver cancer treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14782","type":"journal-article","created":{"date-parts":[[2021,1,2]],"date-time":"2021-01-02T07:59:11Z","timestamp":1609574351000},"page":"1131-1147","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Tribbles homolog 2 promotes hepatic fibrosis and hepatocarcinogenesis through phosphatase 1A\u2010Mediated stabilization of yes\u2010associated protein"],"prefix":"10.1111","volume":"41","author":[{"given":"Dejuan","family":"Xiang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Bioactive Natural Product Research School of Traditional Chinese Pharmacy China Pharmaceutical University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyun","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Bioactive Natural Product Research School of Traditional Chinese Pharmacy China Pharmaceutical University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanqiu","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Bioactive Natural Product Research School of Traditional Chinese Pharmacy China Pharmaceutical University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Zou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Bioactive Natural Product Research School of Traditional Chinese Pharmacy China 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