ETV5 overexpression contributes to tumor growth and progression of thyroid cancer through PIK3CA

被引：21
作者：
Meng, Dongdong [1 ]
Li, Zhifu [2 ]
Ma, Xiaojun [1 ]
Wu, Lina [1 ]
Fu, Lijun [3 ]
Qin, Guijun [1 ]
机构：
[1] Zhengzhou Univ, Affiliated Hosp 1, Dept Endocrinol, 1 Jianshe East Rd, Zhengzhou 450052, Henan, Peoples R China
[2] Zhengzhou Univ, Dept Orthoped Surg, Affiliated Hosp 1, Zhengzhou 450052, Henan, Peoples R China
[3] Zhengzhou Univ, Dept Thyroid Surg, Affiliated Hosp 1, Zhengzhou 450052, Henan, Peoples R China
来源：
LIFE SCIENCES | 2020年 / 253卷
关键词：
ETS variant 5; PIK3CA; Thyroid cancer; Estrogen receptor; Epithelial-mesenchymal transition; TRANSCRIPTION FACTORS ETV4; UP-REGULATION; EXPRESSION; ESTROGEN; PROLIFERATION; INDUCTION;
D O I：
10.1016/j.lfs.2020.117693
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
Aims: Thyroid cancer is a common endocrine malignancy and sex hormone plays an important role in it. We have previously shown that activation of estrogen receptor (ER) alpha promotes thyroid cancer cell proliferation and invasion. Here, we attempted to investigate the role of ETS variant 5 (ETV5) on estrogen drived thyroid malignancy. Main methods: Ten patients with follicular thyroid cancer were enrolled in this study. Cell proliferation and migration ability were analyzed by CCK-8 assay and cell migration assay, respectively. Chromatin immunoprecipitation-PCR and luciferase assay were conducted to analyze the relationship of ETV5 and PIK3CA. Key findings: ETV5 is highly expressed in thyroid tissues from patients with follicular thyroid cancer as well as in FTC133 cells. 17b-estradiol or overexpression of ERa induced an increase in ETV5 protein level in FTC133 cells. Knockdown of ETV5 inhibited FTC133 cell proliferation, migration, and epithelial-mesenchymal transition, while 17b-estradiol could not correct this effect. Additionally, the level of PIK3CA was markedly decreased in ETV5 knockdown cells and had a positive correlation with ETV5 in thyroid cancer patients. Chromatin immunoprecipitation-PCR analysis and luciferase assay confirmed that ETV5 directly targeted PIK3CA and that ETV5 was bound to the promoter region of PIK3CA. In addition, PIK3CA overexpression abrogated ETV5-induced cell growth, migration and epithelial-mesenchymal transition. Significance: ETV5 enhanced cell proliferation, migration, and epithelial-mesenchymal transition through the PIK3CA signaling pathway, indicating that ETV5 may be a therapeutic target in thyroid cancer.
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页数：7
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