{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T03:39:49Z","timestamp":1784864389142,"version":"3.55.0"},"reference-count":43,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,10,24]],"date-time":"2018-10-24T00:00:00Z","timestamp":1540339200000},"content-version":"vor","delay-in-days":0,"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":["81602571"],"award-info":[{"award-number":["81602571"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>14\u20103\u20103<jats:italic>\u03b6<\/jats:italic>, a phosphopeptide\u2010binding molecule, is reportedly overexpressed in the cancerous tissues of patients with hepatocellular carcinoma (<jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content>). Hepatitis B virus (<jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content>) protein X (<jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>x) draws intensive attention in <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content>\u2010related <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> because it not only regulates <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> replication, but also promotes carcinogenesis by interacting with various tumor or antitumor molecules. This study is performed to investigate whether and how 14\u20103\u20103<jats:italic>\u03b6<\/jats:italic> interacts with <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>x. The coimmunoprecipitation (Co\u2010<jats:styled-content style=\"fixed-case\">IP<\/jats:styled-content>) results showed that 14\u20103\u20103<jats:italic>\u03b6<\/jats:italic> bond to <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>x in <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content>\u2010infected Hep3B <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> cells and <jats:styled-content style=\"fixed-case\">CSQT<\/jats:styled-content>\u20102 portal vein tumor thrombosis (<jats:styled-content style=\"fixed-case\">PVTT<\/jats:styled-content>) cells. By performing Co\u2010<jats:styled-content style=\"fixed-case\">IP<\/jats:styled-content> assay in <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content>\u2010free Huh7 cells expressing wild\u2010type <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>x, mutant <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>x\u2010S31A, or <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>x\u2010S31D (serine<jats:sup>31<\/jats:sup> was mutated into alanine<jats:sup>31<\/jats:sup> or aspartic acid<jats:sup>31<\/jats:sup>), we found that the phosphorylated serine<jats:sup>31<\/jats:sup> with its near amino acid residues constituted a <jats:styled-content style=\"fixed-case\">RPL<\/jats:styled-content>phosphoS<jats:sup>31<\/jats:sup><jats:styled-content style=\"fixed-case\">GP<\/jats:styled-content> (R, arginine; P, proline; L, leucine; S, serine; G, glycine) motif in <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>x for 14\u20103\u20103<jats:italic>\u03b6<\/jats:italic> docking. This 14\u20103\u20103<jats:italic>\u03b6<\/jats:italic>\u2010<jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>x interaction was partly impaired when Akt signaling transduction was blocked by <jats:styled-content style=\"fixed-case\">LY<\/jats:styled-content>294002. Furthermore, 14\u20103\u20103<jats:italic>\u03b6<\/jats:italic> silencing augmented <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>x ubiquitination and decreased its expression in cancer cells and xenograft tumor. The migratory and invasive abilities of <jats:styled-content style=\"fixed-case\">CSQT<\/jats:styled-content>\u20102 cells were inhibited upon 14\u20103\u20103<jats:italic>\u03b6<\/jats:italic> silencing, whereas partly restored by <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>x overexpression. Additionally, 14\u20103\u20103<jats:italic>\u03b6<\/jats:italic> positively correlated with <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>x to be overexpressed in the primary <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> tissues (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.344) and metastatic <jats:styled-content style=\"fixed-case\">PVTT<\/jats:styled-content> (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.348). In summary, findings of this study reveal a novel 14\u20103\u20103<jats:italic>\u03b6<\/jats:italic>\u2010<jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>x interaction in <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> cells and suggest 14\u20103\u20103<jats:italic>\u03b6<\/jats:italic> as a candidate target for treating <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content>\u2010related <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content>.<\/jats:p>","DOI":"10.1002\/cam4.1512","type":"journal-article","created":{"date-parts":[[2018,10,25]],"date-time":"2018-10-25T04:08:56Z","timestamp":1540440536000},"page":"5543-5553","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["14\u20103\u20103<i>\u03b6<\/i> binds to hepatitis B virus protein X and maintains its protein stability in hepatocellular carcinoma 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyi","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery The General Hospital of Shenyang Military Area Command  Shenyang 100016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longfei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery The General Hospital of Shenyang Military Area Command  Shenyang 100016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahong","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreas Surgery Beijing Tsinghua Changgung Hospital (BTCH) School of Clinical Medicine Tsinghua University  Beijing 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