{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T03:09:06Z","timestamp":1788923346759,"version":"build-2803163510"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["MedScience"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Hepatocellular carcinoma (HCC) remains a lethal malignancy with limited therapeutic targets. P53 and DNA damage-regulated gene 1 (PDRG1) has emerged as an oncogene in multiple cancers, yet its role and regulatory mechanism in HCC remain unclear. Here, we demonstrated that PDRG1 expression was significantly upregulated in HCC tissues compared to normal liver, correlating with advanced tumor stage, higher grade, and poor patient survival. Functionally, PDRG1 knockdown suppressed HCC cell proliferation, migration, and invasion\n                    <jats:italic>in vitro<\/jats:italic>\n                    and inhibited tumor growth and lung metastasis\n                    <jats:italic>in vivo<\/jats:italic>\n                    , whereas PDRG1 overexpression exerted opposite effects. Mechanistically, PDRG1 activated Wnt\/\u03b2-catenin signaling, elevating levels of \u03b2-catenin, c-Myc, and phosphorylated GSK-3\u03b2, and the oncogenic effects of PDRG1 were reversed by the Wnt pathway inhibitor XAV939. Furthermore, transcription factor Specificity Protein 1 (SP1) bound directly to the PDRG1 promoter at the E3 site (\u20131927 to\u20131917) and activated its transcription. The pro-tumor effects of SP1 were rescued by PDRG1 silencing, indicating that SP1 acts through PDRG1. Collectively, our study identifies SP1 as an upstream transcriptional activator of PDRG1 and defines the SP1\/PDRG1\/Wnt\/\u03b2-catenin axis as a key regulatory pathway promoting HCC progression, suggesting its potential as a prognostic biomarker and therapeutic target.\n                  <\/jats:p>","DOI":"10.1007\/s11684-026-1237-8","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T02:15:24Z","timestamp":1780625724000},"page":"496-514","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PDRG1 induced by SP1 facilitates the proliferation and metastasis of hepatocellular carcinoma by activating the Wnt\/\u03b2-catenin pathway"],"prefix":"10.1007","volume":"20","author":[{"given":"Xudong","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihua","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haikuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyi","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengcheng","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinglin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihui","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changxing","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junqi","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqiang","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfu","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"issue":"3","key":"1237_CR1","first-page":"209","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. 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Written informed consent was obtained from all participants, and all animal procedures followed the institutional and national guidelines for the care and use of laboratory animals.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethics guidelines"}}]}}