EZH2 upregulation by ERα induces proliferation and migration of papillary thyroid carcinoma
Liqiong Xue,
Hongzhu Yan,
Ying Chen,
Qifa Zhang,
Xin Xie,
Xiaoying Ding,
Xiaojing Wang,
Zhongqing Qian,
Feng Xiao,
Zhiyi Song,
Yijie Wu,
Yongde Peng,
Huanbai Xu
Affiliations
Liqiong Xue
Department of Endocrinology and Metabolism, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University
Hongzhu Yan
Department of Pathology, Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine
Ying Chen
Department of Endocrinology and Metabolism, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University
Qifa Zhang
Department of Urology, Department of Endocrinology and Metabolism, Shanghai Traditional Chinese Medicine-Integrated hospital, Shanghai university of Traditional Chinese Medicine
Xin Xie
Department of Urology, Department of Endocrinology and Metabolism, Shanghai Traditional Chinese Medicine-Integrated hospital, Shanghai university of Traditional Chinese Medicine
Xiaoying Ding
Department of Endocrinology and Metabolism, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University
Xiaojing Wang
Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease, Bengbu Medical College
Zhongqing Qian
Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease, Bengbu Medical College
Feng Xiao
Department of Pathology, Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine
Zhiyi Song
Department of Endocrinology and Metabolism, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University
Yijie Wu
Department of Endocrinology and Metabolism, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University
Yongde Peng
Department of Endocrinology and Metabolism, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University
Huanbai Xu
Department of Endocrinology and Metabolism, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University
Abstract Background The incidence of papillary thyroid carcinoma (PTC) has been increasing worldwide in recent years. Therefore, novel potential therapeutic targets for PTC are urgently needed. Enhancer of zeste homolog 2 (EZH2), a methyltransferase belonging to PRC2, plays important roles in epigenetic silencing and cell cycle regulation. EZH2 overexpression has been found in several malignant tumor tissues, while its expression and function in PTC are largely unknown. Methods Sixty-five cases of PTC tissue confirmed by pathology and 30 cases of normal thyroid tissue adjacent to PTC tissue were collected from patients undergoing surgical treatment, between February 2003 and February 2006. We investigated the clinic pathologic significance of EZH2 expression using Realtime-PCR and IHC in 65 human PTC tissues and 30 normal thyroid tissue samples. The EZH2 expression in human PTC cell lines (K1 and W3) and the normal thyroid follicular epithelial cell line Nthy-ori 3–1 was analyzed by Western blotting and Realtime PCR. The expressions of ERα and ERβ in cell lines were analyzed by Realtime PCR.The tumor cell biological behavior was evaluated by CCK8 assay, colony formation assay, transwell migration assay and xenograft tumors model. Results Higher rate of EZH2 expression was found in PTC tissues than in normal thyroid tissues, EZH2 expression is associated with lymph node metastasis and recurrent. Inhibition of EZH2 in PTC cell lines downregulates cellular proliferation and migration. PTC is a disease with high incidence of female and E2-ERα upregulates EZH2 expression. Conclusions These results suggest a potential role of EZH2 for the PTC growth and metastasis. As a novel therapy, a pharmacological therapy targeting EZH2 has full potential in treatment of PTC.
