{"title":"RNF216通过促进p53泛素化抑制肺腺癌铁下垂。","authors":"Jiasheng Wu, Weiqiang Mo, Haiqin Wang, Jianping Jiang, Jing Zhao","doi":"10.1177/09603271251336793","DOIUrl":null,"url":null,"abstract":"<p><p>PurposeLung adenocarcinoma (LUAD) is the most prevalent subtype of non-small cell lung cancer and a leading cause of cancer-related mortality worldwide. This study investigates the role of Ring Finger Protein 216 (RNF216) in LUAD progression.MethodsRNF216 expression was evaluated in LUAD tissues and cells. Functional assays evaluated cell viability, migration, invasion, and ferroptosis <i>in vitro</i>. Mechanistic investigations defined RNF216's role in regulating p53 ubiquitination and stability. <i>In vivo</i>, xenograft models evaluated tumor growth and ferroptosis.ResultsRNF216 was markedly overexpressed in LUAD tissues and cell lines. Functional studies demonstrated that silencing RNF216 suppressed LUAD cell proliferation, migration, and invasion while inducing ferroptosis, characterized by increased reactive oxygen species (ROS), lipid peroxidation (LPO), and intracellular Fe<sup>2+</sup> accumulation. Mechanistically, RNF216 knockdown stabilized p53 by reducing its ubiquitination, thereby promoting ferroptosis. These findings were corroborated <i>in vivo</i>, where RNF216 silencing significantly inhibited tumor growth and enhanced ferroptosis in xenograft models.ConclusionsOur results establish RNF216 as a pivotal oncogenic driver that accelerates LUAD progression by suppressing ferroptosis through p53 ubiquitination. Targeting RNF216 may represent a promising therapeutic strategy to induce ferroptosis and combat LUAD.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251336793"},"PeriodicalIF":3.2000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"RNF216 inhibits ferroptosis in lung adenocarcinoma by promoting p53 ubiquitination.\",\"authors\":\"Jiasheng Wu, Weiqiang Mo, Haiqin Wang, Jianping Jiang, Jing Zhao\",\"doi\":\"10.1177/09603271251336793\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>PurposeLung adenocarcinoma (LUAD) is the most prevalent subtype of non-small cell lung cancer and a leading cause of cancer-related mortality worldwide. This study investigates the role of Ring Finger Protein 216 (RNF216) in LUAD progression.MethodsRNF216 expression was evaluated in LUAD tissues and cells. Functional assays evaluated cell viability, migration, invasion, and ferroptosis <i>in vitro</i>. Mechanistic investigations defined RNF216's role in regulating p53 ubiquitination and stability. <i>In vivo</i>, xenograft models evaluated tumor growth and ferroptosis.ResultsRNF216 was markedly overexpressed in LUAD tissues and cell lines. Functional studies demonstrated that silencing RNF216 suppressed LUAD cell proliferation, migration, and invasion while inducing ferroptosis, characterized by increased reactive oxygen species (ROS), lipid peroxidation (LPO), and intracellular Fe<sup>2+</sup> accumulation. Mechanistically, RNF216 knockdown stabilized p53 by reducing its ubiquitination, thereby promoting ferroptosis. These findings were corroborated <i>in vivo</i>, where RNF216 silencing significantly inhibited tumor growth and enhanced ferroptosis in xenograft models.ConclusionsOur results establish RNF216 as a pivotal oncogenic driver that accelerates LUAD progression by suppressing ferroptosis through p53 ubiquitination. Targeting RNF216 may represent a promising therapeutic strategy to induce ferroptosis and combat LUAD.</p>\",\"PeriodicalId\":94029,\"journal\":{\"name\":\"Human & experimental toxicology\",\"volume\":\"44 \",\"pages\":\"9603271251336793\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Human & experimental toxicology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1177/09603271251336793\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/6/12 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human & experimental toxicology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/09603271251336793","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/12 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
RNF216 inhibits ferroptosis in lung adenocarcinoma by promoting p53 ubiquitination.
PurposeLung adenocarcinoma (LUAD) is the most prevalent subtype of non-small cell lung cancer and a leading cause of cancer-related mortality worldwide. This study investigates the role of Ring Finger Protein 216 (RNF216) in LUAD progression.MethodsRNF216 expression was evaluated in LUAD tissues and cells. Functional assays evaluated cell viability, migration, invasion, and ferroptosis in vitro. Mechanistic investigations defined RNF216's role in regulating p53 ubiquitination and stability. In vivo, xenograft models evaluated tumor growth and ferroptosis.ResultsRNF216 was markedly overexpressed in LUAD tissues and cell lines. Functional studies demonstrated that silencing RNF216 suppressed LUAD cell proliferation, migration, and invasion while inducing ferroptosis, characterized by increased reactive oxygen species (ROS), lipid peroxidation (LPO), and intracellular Fe2+ accumulation. Mechanistically, RNF216 knockdown stabilized p53 by reducing its ubiquitination, thereby promoting ferroptosis. These findings were corroborated in vivo, where RNF216 silencing significantly inhibited tumor growth and enhanced ferroptosis in xenograft models.ConclusionsOur results establish RNF216 as a pivotal oncogenic driver that accelerates LUAD progression by suppressing ferroptosis through p53 ubiquitination. Targeting RNF216 may represent a promising therapeutic strategy to induce ferroptosis and combat LUAD.