{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:04:22Z","timestamp":1785420262347,"version":"3.56.0"},"reference-count":46,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Intramural Research Program of the National Institutes of Health"},{"name":"National Cancer Institute"},{"id":[{"id":"https:\/\/ror.org\/02t771148","id-type":"ROR","asserted-by":"publisher"}]},{"name":"CCR"},{"id":[{"id":"https:\/\/ror.org\/01chgch18","id-type":"ROR","asserted-by":"publisher"}]},{"name":"CIL"},{"id":[{"id":"https:\/\/ror.org\/011724532","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Hepatocellular carcinoma (HCC) remains a major malignancy with high incidence and mortality, in part due to its diverse etiology and intratumoral heterogeneity, which contributes to drug resistance and frequent recurrence. SALL1 (Spalt-Like Transcription Factor 1), a zinc-finger transcription factor, was reported to function as a tumor suppressor in several cancers, including breast cancer and glioma, and accumulating evidence support its involvement in tumor biology. In this study, the role of SALL1 in HCC was examined. Methods: Public RNA and protein databases derived from human HCC were interrogated. Western blotting quantification of clinical HCC for SALL1 levels was carried out. Cell culture and xenograft studies were performed using genetically modified HCC tumor cells. Results: As revealed by pubic RNA and protein database analysis and further western blotting quantification of clinical samples of HCC, SALL1 is decreased in human HCC. The effect of reduced SALL1 expression on the tumorigenic properties and transcriptional regulation in HCC was then examined. Knockdown of SALL1 in the HCC cell lines Huh7 and Hep3B, enhanced cell proliferation in vitro and accelerated tumor growth in a xenograft mouse model, suggesting that lower SALL1 expression increases cell proliferation and tumorigenesis in HCC. RNA-seq and ChIP analyses further identified three novel candidate target genes (SLC6A14, GABRG1, and AKR1B10), suggesting that SALL1 may exert a tumor-suppressive effect, at least in part, through negative regulation of these genes. Conclusions: These findings establish SALL1 as a possible tumor suppressor and provide new insights into the biological significance of SALL1 downregulation in HCC. SALL1 could be a candidate prognostic marker and a potential therapeutic target.<\/jats:p>","DOI":"10.3390\/cancers18091355","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T12:29:11Z","timestamp":1777033751000},"page":"1355","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Loss of SALL1 Promotes Hepatocellular Carcinoma Growth and Is Associated with Poor Clinical Outcome"],"prefix":"10.3390","volume":"18","author":[{"given":"Yoshifumi","family":"Saito","sequence":"first","affiliation":[{"name":"Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"},{"name":"Laboratory of Metabolism, Division of Molecular Science, Graduate School of Science and Technology, Gunma University, Kiryu 376-8515, Gunma, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6684-7472","authenticated-orcid":false,"given":"Carlos Ichiro","family":"Kasano-Camones","sequence":"additional","affiliation":[{"name":"Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsumi","family":"Tamura","sequence":"additional","affiliation":[{"name":"Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shioko","family":"Kimura","sequence":"additional","affiliation":[{"name":"Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8886-4433","authenticated-orcid":false,"given":"Xiaoting","family":"Yu","sequence":"additional","affiliation":[{"name":"Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"Cui","sequence":"additional","affiliation":[{"name":"Key Laboratory of Remodeling-Related Cardiovascular Diseases, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Ministry of Education, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vorthon","family":"Sawaswong","sequence":"additional","affiliation":[{"name":"Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristopher W.","family":"Krausz","sequence":"additional","affiliation":[{"name":"Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Beijing Friendship Hospital, National Clinical Research Center for Digestive Diseases, State Key Laboratory of Digestive Health, Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Capital Medical University, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6661-1953","authenticated-orcid":false,"given":"Aijuan","family":"Qu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Remodeling-Related Cardiovascular Diseases, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Ministry of Education, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9710-7482","authenticated-orcid":false,"given":"Yusuke","family":"Inoue","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolism, Division of Molecular Science, Graduate School of Science and Technology, Gunma University, Kiryu 376-8515, Gunma, Japan"},{"name":"Center for Food Science and Wellness, Gunma University, Maebashi 371-8510, Gunma, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shogo","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank J.","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"ref_1","first-page":"394","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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