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BRAF-induced EHF Expression Affects TERT in Aggressive Papillary Thyroid Cancer

文献类型：期刊论文

作者Xu, Yiyi8; Gao, Jiwei1,8; Wang, Na2; Zedenius, Jan3,4; Nilsson, Inga-Lena3,4; Lui, Weng-Onn8; Xu, Dawei5; Juhlin, C. Christofer6,8; Larsson, Catharina8; Mu, Ninni7,8
刊名JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
出版日期2024-09-16
关键词EHF TERT promoter mutation BRAF(V600E) thyroid carcinoma prognosis
ISSN号0021-972X
DOI10.1210/clinem/dgae589
通讯作者Larsson, Catharina(catharina.larsson@ki.se) ; Mu, Ninni(ninni.mu@ki.se)
英文摘要Context: BRAF(V600E) and TERT promoter mutations in papillary thyroid carcinoma (PTC) have a synergistic effect on prognosis. This effect is believed to arise from MAPK activation triggered by BRAF(V600E), leading to the upregulation of ETS transcription factors that bind to the mutant TERT promoter. Objectives: To explore the role of ETS factors in relation to clinical features, BRAF(V600E), and TERT promoter mutations in PTC. Design: Transcriptomic data for 28 ETS factors were analyzed in the PTC cohort of The Cancer Genome Atlas (n = 399) and subsequently validated in a local cohort (n = 93). In vitro experiments were performed to investigate the regulatory role in relation to BRAF(V600E) and TERT expression. Results: The Cancer Genome Atlas identified ETS1, ERG, FLI1, GABPA, EHF, ETV6, and SPDEF as differentially expressed genes between stages I + II and III + IV. In both cohorts, EHF was consistently associated with adverse clinical features, BRAF(V600E) and TERT promoter mutation/expression. Notably, in BRAF(V600E) mutated PTC, high EHF expression was associated with shorter disease-free survival. Cases harboring concurrent BRAF(V600E), TERT promoter mutations, and high EHF expression exhibited the shortest disease-free survival. In cells harboring concurrent BRAF(V600E) and TERT promoter mutation, overexpression of EHF significantly increased TERT expression, whereas knockdown or pharmacological inhibition of BRAF significantly decreased both EHF and TERT expression. In addition, chromatin immunoprecipitation and quantitative PCR analysis suggested a potential binding of EHF in TERT promoter mutant cells but not in TERT promoter wild-type cells. Conclusion: The ETS transcription factor EHF is associated with poor prognosis in PTC. This is potentially mediated by BRAF-induced upregulation of EHF, which in turn increases TERT expression in TERT promoter mutated cells.
WOS关键词PROMOTER MUTATIONS ; TRANSCRIPTION FACTORS ; ACQUIRED-RESISTANCE ; SMALL-MOLECULE ; V600E ; VEMURAFENIB ; PREVALENCE ; INHIBITORS ; YK-4-279 ; SWITCH
资助项目Swedish Cancer Society[080500] ; Swedish Research Council[2021-03006] ; Cancer Research Funds at Radiumhemmet[204103] ; Stockholm County Council[RS2021-0855] ; Karolinska Institutet ; China Scholarship Council ; Swedish Research Council[2021-03006]
WOS研究方向Endocrinology & Metabolism
语种英语
WOS记录号WOS:001313077200001
出版者ENDOCRINE SOC
资助机构Swedish Cancer Society ; Swedish Research Council ; Cancer Research Funds at Radiumhemmet ; Stockholm County Council ; Karolinska Institutet ; China Scholarship Council ; Swedish Research Council
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/135260]  
专题中国科学院合肥物质科学研究院
通讯作者Larsson, Catharina; Mu, Ninni
作者单位1.Univ Chinese Acad Sci, Canc Hosp, Zhejiang Canc Hosp, Hangzhou 310022, Peoples R China
2.Karolinska Inst, Dept Med Huddinge, SE-14183 Stockholm, Sweden
3.Karolinska Inst, Dept Mol Med & Surg, SE-17176 Stockholm, Sweden
4.Karolinska Univ Hosp, Dept Breast Endocrine Tumors & Sarcoma, SE-17164 Stockholm, Sweden
5.Karolinska Inst, Dept Med Solna, SE-17176 Stockholm, Sweden
6.Karolinska Univ Hosp, Dept Pathol & Canc Diagnost, SE-17164 Stockholm, Sweden
7.Karolinska Univ Hosp, Clin Genet, SE-17176 Stockholm, Sweden
8.Karolinska Inst, Dept Oncol Pathol, BioClin J6 20, SE-17164 Stockholm, Sweden
推荐引用方式
GB/T 7714		 Xu, Yiyi,Gao, Jiwei,Wang, Na,et al. BRAF-induced EHF Expression Affects TERT in Aggressive Papillary Thyroid Cancer[J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM,2024.
APA Xu, Yiyi.,Gao, Jiwei.,Wang, Na.,Zedenius, Jan.,Nilsson, Inga-Lena.,...&Mu, Ninni.(2024).BRAF-induced EHF Expression Affects TERT in Aggressive Papillary Thyroid Cancer.JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM.
MLA Xu, Yiyi,et al."BRAF-induced EHF Expression Affects TERT in Aggressive Papillary Thyroid Cancer".JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2024).

入库方式： OAI收割

来源：合肥物质科学研究院

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