title: Increased expression of EHF contributes to thyroid tumorigenesis through transcriptionally regulating HER2 and HER3.
abstract: E26 transformation-specific (ETS) transcription factor EHF plays a tumor suppressor role in prostate cancer and esophageal squamous cell carcinoma (ESCC), whereas it is overexpressed and may act as an oncogene in ovarian and mammary cancers. However, its biological role in thyroid cancer remains totally unknown. The aim of this study was to explore the biological functions of EHF and its potential as a therapeutic target in thyroid cancer. Using quantitative RT-PCR (qRT-PCR) assay, we evaluated mRNA expression of EHF in a cohort of primary papillary thyroid cancers (PTCs) and matched non-cancerous thyroid tissues. The functions of knockdown and ectopic expression of EHF in thyroid cancer cells were determine by a series of in vitro and in vivo experiments. Moreover, dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays were performed to identify its downstream targets. Our data showed that EHF expression was significantly increased in PTCs compared with matched non-cancerous thyroid tissues. EHF knockdown significantly inhibited thyroid cancer cell proliferation, colony formation, migration, invasion and tumorigenic potential in nude mice and induced cell cycle arrested and apoptosis by modulating the PI3K/Akt and MAPK/Erk signaling pathways. On the other hand, ectopic expression of EHF in thyroid cancer cells notably promoted cell growth and invasiveness. Importantly, EHF was identified as a new transcription factor for HER2 and HER3, contributing to thyroid tumorigenesis. Altogether, our findings suggest that EHF is a novel functional oncogene in thyroid cancer by transcriptionally regulating HER2 and HER3, and may represent a potential therapeutic target for this cancer.
authors: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.|Department of Rheumatology, Xi'an No 5 Hospital, Xi'an 710082, P.R. China.
authors: Yanyan
authors: Y
authors: Lv
authors: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors: Fang
authors: F
authors: Sui
authors: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors: Jingjing
authors: J
authors: Ma
authors: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors: Xiaojuan
authors: X
authors: Ren
authors: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.|Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors: Qi
authors: Q
authors: Yang
authors: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors: Yanfang
authors: Y
authors: Zhang
authors: Department of Endocrinology and Metabolism, The First Affiliated Hospital of China Medical University, Shenyang 110001, P.R. China.
authors: Haixia
authors: H
authors: Guan
authors: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.|Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors: Bingyin
authors: B
authors: Shi
authors: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.|Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors: Peng
authors: P
authors: Hou
authors: Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.|Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors: Meiju
authors: M
authors: Ji
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002465:Cell Movement; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D014157:Transcription Factors; C403306:EHF protein, human; C508053:ERBB2 protein, human; C581292:ERBB3 protein, human
keywords: EHF; HER family of receptor tyrosine kinases; MAPK pathway; PI3K/Akt pathway; thyroid cancer