The relationship between EZH2 methylation and thyroid cancer differentiation-related markers and its therapeutic value
10.19405/j.cnki.issn1000-1492.2025.04.015
- Author:
Lin Jing
1
;
Qi Jiang
2
;
Jiangning Gu
3
;
Haifeng Luo
4
;
Xiaoyi Guo
4
;
Tianci Shen
4
;
Zihao Dai
4
;
Dan Chen
1
Author Information
1. Dept of Pathology，The First Hospital of Dalian Medical University，Dalian 116011
2. Dept of Pathology，Affiliated Zhongshan Hospital of Dalian University，Dalian 116001
3. Dept of Endoscopy，General Hospital of Northern Theater Command，Shenyang 110016
4. Dept of General Surgery，The First Hospital of Dalian Medical University，Dalian 116011
- Publication Type:Journal Article
- Keywords:
EZH2;
H3K27me3;
anaplastic thyroid cancer;
dedifferentiation;
methylation;
GSK126
- From:
Acta Universitatis Medicinalis Anhui
2025;60(4):691-696, 706
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To investigate the role of enhancer of zeste homolog 2(EZH2)-trimethylated lysine 27 of histone H3(H3K27me3) axis in the dedifferentiation of thyroid cancer and its clinical value as a potential target for the treatment of anaplastic thyroid cancer(ATC).
Methods : Immunohistochemical SP method was used to detect the expression of EZH2, H3K27me3, paired box gene 8(PAX8), thyroglobulin(TG) and thyroid transcription factor 1(TTF1) in ATC and papillary thyroid carcinoma(PTC) and their adjacent tissues. The relationship between EZH2 and thyroid differentiation markers(PAX8, TTF1, TG) was further analyzed by gene expression omnibus(GEO) database. ATC cell lines 8305C and BHT-101 were culturedin vitro. Real-time reverse transcription PCR(RT-qPCR) was used to detect the expression of thyroid differentiation markers(TTF1, PAX8) mRNA in ATC cell lines treated with EZH2 inhibitor(GSK126), and evaluate the potential therapeutic effect of GSK126in vitro. The effects of GSK126 and BRAF inhibitor vemurafenib on the proliferation of ATC cell lines were observed by cell proliferation assay.
Results :The expression of EZH2 in ATC tissues was significantly higher than that in papillary thyroid carcinoma and adjacent tissues(P<0.05). The expression of H3K37me3 in ATC tissues was significantly lower than that in PTC tissues(P<0.05). EZH2 was negatively correlated with PAX8 and TG expression levels, but not with TTF1 expression level.In vitroexperiments, GSK126 could reverse the expression of thyroid differentiation markers PAX8 and TTF1 in ATC cell lines. GSK126 combined with BRAF inhibitor vemurafenib could significantly inhibit the growth of ATC cell lines.
Conclusion:The EZH2-H3K27me3 axis plays an important role in regulating thyroid specific markers, and the inhibition of EZH2 by small molecular compounds is a promising target for ATC treatment in the future.
- Full text:2026012711145599427EZH2甲基化与甲状腺癌分...志物的关系及治疗价值的研究_荆琳.pdf
