Research Papers:

Increased expression of EHF contributes to thyroid tumorigenesis through transcriptionally regulating HER2 and HER3

Yanyan Lv, Fang Sui, Jingjing Ma, Xiaojuan Ren, Qi Yang, Yanfang Zhang, Haixia Guan, Bingyin Shi, Peng Hou and Meiju Ji _

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Oncotarget. 2016; 7:57978-57990. https://doi.org/10.18632/oncotarget.11154

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Yanyan Lv1,2, Fang Sui1, Jingjing Ma1, Xiaojuan Ren1, Qi Yang1,3, Yanfang Zhang1, Haixia Guan4, Bingyin Shi1,3, Peng Hou1,3, Meiju Ji3,5

1Department of Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, P.R. China

2Department of Rheumatology, Xi’an No 5 Hospital, Xi’an 710082, P.R. China

3Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, P.R. China

4Department of Endocrinology and Metabolism, The First Affiliated Hospital of China Medical University, Shenyang 110001, P.R. China

5Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, P.R. China

Correspondence to:

Peng Hou, email: [email protected]

Meiju Ji, email: [email protected]

Keywords: thyroid cancer, EHF, PI3K/Akt pathway, MAPK pathway, HER family of receptor tyrosine kinases

Received: February 09, 2016     Accepted: July 27, 2016     Published: August 09, 2016


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.

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