{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:54:57Z","timestamp":1790268897373,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T00:00:00Z","timestamp":1714176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy characterized by a poor prognosis and closely linked to tumor stemness. However, the key molecules that regulate ICC stemness remain elusive. Although Y\u2010box binding protein 1 (YBX1) negatively affects prognosis in various cancers by enhancing stemness and chemoresistance, its effect on stemness and cisplatin sensitivity in ICC remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Three bulk and single\u2010cell RNA\u2010seq datasets were analyzed to investigate YBX1 expression in ICC and its association with stemness. Clinical samples and colony\/sphere formation assays validated the role of YBX1 in stemness and sensitivity to cisplatin. AZD5363 and KYA1979K explored the interaction of YBX1 with the phosphatidylinositol 3\u2010kinase (PI3K)\/protein kinase B (PKB\/AKT) and WNT\/\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010catenin pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      YBX1 was significantly upregulated in ICC, correlated with worse overall survival and shorter postoperative recurrence time, and was higher in chemotherapy\u2010non\u2010responsive ICC tissues. The YBX1\u2010high group exhibited significantly elevated stemness scores, and genes linked to YBX1 upregulation were enriched in multiple stemness\u2010related pathways. Moreover, YBX1 expression is significantly correlated with several stemness\u2010related genes (\n                      <jats:italic>SOX9<\/jats:italic>\n                      ,\n                      <jats:italic>OCT4<\/jats:italic>\n                      ,\n                      <jats:italic>CD133<\/jats:italic>\n                      ,\n                      <jats:italic>CD44<\/jats:italic>\n                      and\n                      <jats:italic>EPCAM<\/jats:italic>\n                      ). Additionally, YBX1 overexpression significantly enhanced the colony\u2010 and spheroid\u2010forming abilities of ICC cells, accelerated tumor growth\n                      <jats:italic>in vivo<\/jats:italic>\n                      and reduced their sensitivity to cisplatin. Conversely, the downregulation of YBX1 exerted the opposite effect. The transcriptomic analysis highlighted the link between YBX1 and the PI3K\/AKT and WNT\/\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010catenin pathways. Further, AZD5363 and KYA1979K were used to clarify that YBX1 promoted ICC stemness through the regulation of the AKT\/\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010catenin axis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      YBX1 is upregulated in ICC and promotes stemness and cisplatin insensitivity via the AKT\/\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010catenin axis. Our study describes a novel potential therapeutic target for improving ICC prognosis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jgm.3689","type":"journal-article","created":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T03:06:10Z","timestamp":1714187170000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["YBX1 promotes stemness and cisplatin insensitivity in intrahepatic cholangiocarcinoma via the AKT\/\n                    <i>\u03b2<\/i>\n                    \u2010catenin axis"],"prefix":"10.1002","volume":"26","author":[{"given":"Xiaodong","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Hepatic Surgery II, the Eastern Hepatobiliary Surgery Hospital Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiliang","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Hepatic 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