{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T06:24:14Z","timestamp":1786947854968,"version":"build-2736575974"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Uterine corpus endometrial carcinoma (UCEC) is one of the most common gynecological malignancies, and its progression is closely associated with dysregulated protein homeostasis and metabolic reprogramming. TRIM21 is an E3 ubiquitin ligase implicated in tumor regulation, but its role in UCEC remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Datasets from TCGA, CPTAC, and GEO were used to assess the expression pattern, clinical significance, and cellular distribution of TRIM21 in UCEC. TRIM21 expression was validated by immunohistochemistry, qRT-PCR, western blotting, and immunofluorescence. Gain-of-function assays, including CCK-8, colony formation, Transwell migration, apoptosis assays, lipid droplet staining, and xenograft experiments, were performed to determine the biological effects of TRIM21. Quantitative proteomics, immunoprecipitation coupled with mass spectrometry, co-immunoprecipitation, cycloheximide chase, ubiquitination assays, and rescue experiments were conducted to investigate the underlying mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TRIM21 was significantly downregulated in UCEC tissues and cell lines and was associated with favorable prognosis and less aggressive clinicopathological features. TRIM21 overexpression inhibited proliferation, migration, lipid droplet accumulation, and tumor growth, while promoting apoptosis. Mechanistically, SOAT1 was identified as a novel interacting protein of TRIM21. TRIM21 negatively regulated SOAT1 by promoting its K48-linked ubiquitination and proteasomal degradation, thereby reducing SOAT1 protein stability. Restoration of SOAT1 partially reversed the inhibitory effects of TRIM21 on malignant phenotypes and its pro-apoptotic effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TRIM21 functions as a tumor suppressor in UCEC by promoting K48-linked ubiquitination and degradation of SOAT1. These findings reveal a novel mechanism linking protein homeostasis to lipid metabolic regulation in UCEC and suggest that TRIM21 and SOAT1 may serve as potential biomarkers and therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1863307","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T05:25:37Z","timestamp":1786944337000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["TRIM21 suppresses uterine corpus endometrial carcinoma progression by promoting K48 -linked ubiquitination and degradation of SOAT1"],"prefix":"10.3389","volume":"17","author":[{"given":"Hongwei","family":"Chen","sequence":"first","affiliation":[{"name":"Fuyang Medical College, Fuyang Normal University","place":["Fuyang, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Cui","sequence":"additional","affiliation":[{"name":"Fuyang 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