{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:10:36Z","timestamp":1760058636319,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NCI\/NIH","award":["T32-CA229102","5T32-GM008361","5RO1CA276683","P30 AR048311","P20 AI027767","S10OD032422-1"],"award-info":[{"award-number":["T32-CA229102","5T32-GM008361","5RO1CA276683","P30 AR048311","P20 AI027767","S10OD032422-1"]}]},{"name":"UAB Comprehensive Flow Cytometry Core","award":["T32-CA229102","5T32-GM008361","5RO1CA276683","P30 AR048311","P20 AI027767","S10OD032422-1"],"award-info":[{"award-number":["T32-CA229102","5T32-GM008361","5RO1CA276683","P30 AR048311","P20 AI027767","S10OD032422-1"]}]},{"name":"UAB Genomics Core","award":["T32-CA229102","5T32-GM008361","5RO1CA276683","P30 AR048311","P20 AI027767","S10OD032422-1"],"award-info":[{"award-number":["T32-CA229102","5T32-GM008361","5RO1CA276683","P30 AR048311","P20 AI027767","S10OD032422-1"]}]},{"name":"Kaul Pediatric Research Foundation and Destiny StrongER","award":["T32-CA229102","5T32-GM008361","5RO1CA276683","P30 AR048311","P20 AI027767","S10OD032422-1"],"award-info":[{"award-number":["T32-CA229102","5T32-GM008361","5RO1CA276683","P30 AR048311","P20 AI027767","S10OD032422-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hepatoblastoma (HB) is the most common pediatric primary liver tumor. About 20% of affected children have pulmonary metastasis at presentation. Survival rates for these children are dismal, not exceeding 25%. To study this subset of patients, we sequenced a metastatic HB cell line, HLM_2, and identified downregulation of the Liver X Receptor (LXR)\/Retinoid X Receptor (RXR) pathway. LXR\/RXRs function as transcriptional regulators that influence genes implicated in HB development, including the Wnt\/\u03b2-catenin signaling pathway. We assessed the effects of a novel LXR\/RXR agonist, UAB116, on metastatic HB, hypothesizing that this compound would affect genes governing the Wnt\/\u03b2-catenin pathway, decreasing the metastatic phenotype of HLM_2 metastatic HB cells. We evaluated its effects on viability, proliferation, stemness, clonogenicity, and motility, and performed RNA sequencing to study differential gene regulation. Treatment with UAB116 for 72 h decreased HLM_2 proliferation, stemness, clonogenicity, and invasion. RNA sequencing identified an eight-fold increase in TRIM29, a gene known to inhibit \u03b2-catenin, in cells treated with UAB116. Administration of the LXR\/RXR agonist, UAB116, reduces proliferation, stemness, and invasiveness of metastatic HB cells, potentially by upregulation of TRIM29, a known modulator of the Wnt\/\u03b2-catenin pathway, providing support for further exploration of LXR\/RXR agonism as a therapeutic strategy for metastatic HB.<\/jats:p>","DOI":"10.3390\/ijms26093933","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T20:24:52Z","timestamp":1745353492000},"page":"3933","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Novel Rexinoid Agonist, UAB116, Decreases Metastatic Phenotype in Hepatoblastoma by Inhibiting the Wnt\/\u03b2-Catenin Pathway via Upregulation of TRIM29"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1334-7073","authenticated-orcid":false,"given":"Swatika","family":"Butey","sequence":"first","affiliation":[{"name":"Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2729-8244","authenticated-orcid":false,"given":"Morgan L.","family":"Brown","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8213-443X","authenticated-orcid":false,"given":"Janet R.","family":"Julson","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2848-3927","authenticated-orcid":false,"given":"Raoud","family":"Marayati","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0085-0403","authenticated-orcid":false,"given":"Venkatram R.","family":"Atigadda","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryam G.","family":"Shaikh","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nazia","family":"Nazam","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7853-3948","authenticated-orcid":false,"given":"Colin H.","family":"Quinn","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sorina","family":"Shirley","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3952-1017","authenticated-orcid":false,"given":"Laura L.","family":"Stafman","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4613-0527","authenticated-orcid":false,"given":"Elizabeth A.","family":"Beierle","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"29763","DOI":"10.1002\/pbc.29763","article-title":"Incidence and 5-Year Survival of Children and Adolescents with Hepatoblastoma in the United States","volume":"69","author":"Kahla","year":"2022","journal-title":"Pediatr. 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