Abstract
BackgroundThe 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.MethodsSixty-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.ResultsHigher 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.ConclusionsThese 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.
Highlights
The incidence of papillary thyroid carcinoma (PTC) has been increasing worldwide in recent years
Human tissue samples 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 Shanghai General Hospital and Shanghai Seventh People’s Hospital, between February 2003 and February 2006
Enhancer of zeste homolog 2 (EZH2) is upregulated in clinical PTC tissue and cell lines To explore the EZH2 function in human PTC progression, we tried to study the association between its expression and clinicopathological features of PTC
Summary
The incidence of papillary thyroid carcinoma (PTC) has been increasing worldwide in recent years. 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. Polycomb group (PcG) protein plays key roles in regulating cell proliferation and differentiation. As a member of the PcG family and the core catalytic component of the polycomb repressive complex 2 (PRC2), Enhancer of zeste homolog 2 (EZH2) acts by catalyzing trimethylation on histone 3 lysine 27 (H3K27me3) which results the silencing of its target genes [4]. More and more evidences show that EZH2 is involved in diverse fundamental cell processes, including cell proliferation and differentiation, cell cycle regulation and fate decision, Xue et al BMC Cancer (2019) 19:1094 tumorigenesis, cancer stem cell maintenance, and drug resistance [5,6,7,8,9]. EZH2 expression and function in carcinogenesis and tumor progression of PTC has not yet been clarified
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