{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:12:52Z","timestamp":1788415972266,"version":"build-2803163510"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"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. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the expression of SYTL5 in differentiated thyroid carcinoma (DTC) and elucidate its clinical significance and underlying molecular mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      SYTL5 expression in 107 paired DTC and adjacent normal tissues was evaluated by immunohistochemistry, qRT-PCR, and Western blot. Associations with clinicopathological variables were assessed using chi-square or Fisher\u2019s exact tests with Benjamini-Hochberg false discovery rate adjustment, and the distant metastasis subgroup was summarized descriptively because only one M1 case was available. Stable SYTL5 knockdown or overexpression DTC cell lines were established using RNA interference and lentiviral transfection. Cell proliferation, apoptosis, invasion, and migration were assessed using EdU staining, flow cytometry, and Transwell assays. A nude mouse subcutaneous xenograft model was constructed to evaluate tumor growth\n                      <jats:italic>in vivo<\/jats:italic>\n                      . Promoter dual-luciferase reporter assays were performed to evaluate transcriptional regulation of SYTL5 by ZNF384.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SYTL5 expression was significantly upregulated in DTC tissues and was positively associated with lymph node metastasis after false discovery rate adjustment. SYTL5 silencing inhibited DTC cell proliferation, invasion, and migration while modestly increasing apoptosis, whereas SYTL5 overexpression exerted opposite effects. Mechanistically, SYTL5 knockdown was associated with reduced TGFBR2 and phosphorylated Smad3 expression without affecting total Smad3 levels, both\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      . Promoter reporter assays demonstrated that ZNF384 suppressed wild-type SYTL5 promoter activity but not mutant promoter activity. ZNF384 overexpression suppressed SYTL5 expression, inhibited malignant phenotypes of DTC cells, and downregulated TGFBR2 and p-Smad3; these effects were partially reversed by SYTL5 overexpression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SYTL5 is associated with DTC progression and lymph node metastasis and functionally supports malignant phenotypes in DTC models. The data support a ZNF384-SYTL5-TGFBR2\/Smad3 regulatory axis, while direct regulation of TGFBR2 by SYTL5 and the contribution of Smad2 or non-canonical pathways require further study. SYTL5 may represent a candidate therapeutic target for DTC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1810543","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:17:00Z","timestamp":1788412620000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["SYTL5 drives malignant progression in differentiated thyroid carcinoma: unveiling its regulatory mechanisms"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiaohui","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Yancheng Third People\u2019s Hospital","place":["Yancheng, China"]},{"name":"Affiliated Hospital 6 of Nantong University","place":["Yancheng, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Yancheng Third People\u2019s 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