{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:09:30Z","timestamp":1782950970342,"version":"3.54.5"},"reference-count":42,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T00:00:00Z","timestamp":1631664000000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773772"],"award-info":[{"award-number":["81773772"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["xtr0118022"],"award-info":[{"award-number":["xtr0118022"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hepatocellular carcinoma (HCC) is the third leading cause of cancer\u2010related deaths worldwide. Overexpression of pleomorphic adenoma gene like\u20102 (PLAGL2) is associated with tumorigenesis. However, its function in HCC is unclear, and there are currently no anti\u2010HCC drugs that target PLAGL2. Drug repositioning may facilitate the development of PLAGL2\u2010targeted drug candidates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The expression of PLAGL2 in HCC clinical tissue samples and HCC cell lines was analyzed by western blotting. The constructed HCC cell models were used to confirm the underlying function of PLAGL2 as a therapeutic target. Multiple in vitro and in vivo assays were conducted to determine the anti\u2010proliferative and apoptosis\u2010inducing effects of selenium sulfide (SeS<jats:sub>2<\/jats:sub>), which is clinically used for the treatment of seborrheic dermatitis and tinea versicolor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PLAGL2 expression was higher in HCC tumor tissues than in normal adjacent tissues. Its overexpression promoted the resistance of HCC cells of mitochondrial apoptosis through the regulation of the downstream C\u2010MET\/STAT3 signaling axis. SeS<jats:sub>2<\/jats:sub> exerted significant anti\u2010proliferative and apoptosis\u2010inducing effects on HCC cells in a PLAGL2\u2010dependent manner. Mechanistically, SeS<jats:sub>2<\/jats:sub> suppressed C\u2010MET\/STAT3, AKT\/mTOR, and MAPK signaling and triggered Bcl\u20102\/Cyto C\/Caspase\u2010mediated intrinsic mitochondrial apoptosis both in vitro and in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our data reveal an important role of PLAGL2 in apoptosis resistance in HCC and highlight the potential of using SeS<jats:sub>2<\/jats:sub> as a PLAGL2 inhibitor in patients with HCC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.536","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T07:29:46Z","timestamp":1631690986000},"source":"Crossref","is-referenced-by-count":26,"title":["Selenium sulfide disrupts the PLAGL2\/C\u2010MET\/STAT3\u2010induced resistance against mitochondrial apoptosis in hepatocellular carcinoma"],"prefix":"10.1002","volume":"11","author":[{"given":"Tianfeng","family":"Yang","sequence":"first","affiliation":[{"name":"School of Pharmacy Health Science Center Xi'an Jiaotong University  Xi'an P. 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