{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T22:23:32Z","timestamp":1785450212255,"version":"3.56.0"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Education Integration Research Development Foundation of Jiangsu College of Nursing","award":["024SH121003"],"award-info":[{"award-number":["024SH121003"]}]},{"name":"Jiangsu Provincial Health Commission Research Project","award":["Z2024044"],"award-info":[{"award-number":["Z2024044"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Despite advancements in thyroid cancer (THCA) treatment, the prognosis for advanced cases remains poor. Cellular senescence is crucial in tumor progression, with <jats:italic>ETS2<\/jats:italic> emerging as a key regulator. However, the role of <jats:italic>ETS2<\/jats:italic> and its interaction with <jats:italic>ZMYND11<\/jats:italic> in THCA is unclear.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Differentially expressed genes (DEGs) connected with cellular senescence were determined from The Cancer Genome Atlas (TCGA)-THCA dataset. Functional analysis, prognostic risk model, and nomogram were then performed to identify <jats:italic>ETS2<\/jats:italic> as a hub gene. The roles of <jats:italic>ETS2<\/jats:italic> and <jats:italic>ZMYND11<\/jats:italic> were explored using Western blotting (WB), co-immunoprecipitation (Co-IP), and quantitative real-time polymerase chain reaction (qRT-PCR). Effects of <jats:italic>ETS2<\/jats:italic> overexpression and knockdown of <jats:italic>ZMYND11<\/jats:italic> on apoptosis, cell proliferation, epithelial-mesenchymal transition (EMT), and mTOR signaling were evaluated. <jats:italic><jats:italic>In vivo<\/jats:italic><\/jats:italic>, a xenograft model was established using Cal-62 cells with or without <jats:italic>ETS2<\/jats:italic> overexpression to assess tumor growth and protein expression.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p><jats:italic>ETS2<\/jats:italic> was notably downregulated in THCA, and its low expression was connected to adverse prognosis. <jats:italic>ETS2<\/jats:italic> overexpression inhibited THCA cell invasion, migration, proliferation, and induced apoptosis. <jats:italic>ETS2<\/jats:italic> also regulated the expression of EMT markers, indicating its role in inhibiting THCA progression. Co-IP analysis showed that ETS2 interacted with ZMYND11. Knockdown of <jats:italic>ZMYND11<\/jats:italic> attenuated the inhibitory effect of <jats:italic>ETS2<\/jats:italic> on THCA cell behavior and mTOR pathway regulation. <jats:italic><jats:italic>In vivo<\/jats:italic><\/jats:italic>, <jats:italic>ETS2<\/jats:italic> overexpression reduced tumor growth and increased <jats:italic>ETS2<\/jats:italic> and <jats:italic>ZMYND11<\/jats:italic> expression in xenograft tumors.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>This study identified the cellular senescence gene <jats:italic>ETS2<\/jats:italic> as a tumor suppressor in THCA, which interacts with <jats:italic>ZMYND11<\/jats:italic> to regulate THCA tumor progression through the mTOR pathway, thereby inhibiting cell senescence. Targeting the <jats:italic>ETS2<\/jats:italic>-<jats:italic>ZMYND1<\/jats:italic> axis may provide new therapeutic strategies and prognostic biomarkers for THCA.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0328881","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T17:41:18Z","timestamp":1757698878000},"page":"e0328881","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["ETS2 targets ZMYND11 to inhibit thyroid cancer progression via the mTOR signaling 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