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丝氨酸蛋白酶抑制剂 2(SERPINE2)反馈调节人甲状腺乳头状癌细胞中的表皮生长因子/表皮生长因子受体(EGF/EGFR)信号通路。

SERPINE2 feedback regulates EGF/EGFR signaling in human papillary thyroid carcinoma cells.

机构信息

Department of Thyroid and Breast Surgery, The Central Hospital of Wuhan, Wuhan, Hubei 430014, P.R. China.

出版信息

Mol Med Rep. 2021 May;23(5). doi: 10.3892/mmr.2021.11981. Epub 2021 Mar 24.

DOI:10.3892/mmr.2021.11981
PMID:33760135
Abstract

Thyroid cancer (TC) is the most prevalent malignant tumor in the endocrine system. Serpin peptidase inhibitor clade E member 2 (SERPINE2) is closely associated with tumor metastasis. The aim of the present study was to investigate whether SERPINE2 forms a feedback loop with epidermal growth factor (EGF)/EGF receptor (EGFR) that regulates cellular processes in human papillary thyroid carcinoma (TPC‑1) cells. Reverse transcription‑quantitative PCR and western blotting were utilized to analyze the expression of SERPINE2. Cell proliferation ability was detected with a cell proliferation and cytotoxicity assay kit (MTT) and by clone formation assay. The proliferation markers, including proliferating cell nuclear antigen and Ki‑67, were also investigated to analyze the proliferative activity of TPC‑1 cells. Besides, cell migration and invasion were analyzed by wound healing and Transwell assays, respectively, while cell apoptosis was analyzed by TUNEL staining. The results showed that SERPINE2 expression was increased in TPC cells, and SERPINE2 and EGF/EGFR regulated each other. Furthermore, SERPINE2 overexpression and silencing regulated TPC cell proliferation, migration, invasion and apoptosis. Besides, an EGFR inhibitor blocked the effects of SERPINE2 overexpression on the aforementioned biological processes. Therefore, the present study confirmed that SERPINE2 formed a positive feedback with EGF/EGFR to regulate the proliferation, invasion and migration of TPC cells, possibly providing novel insights into potential therapeutic targets of papillary TC.

摘要

甲状腺癌 (TC) 是内分泌系统中最常见的恶性肿瘤。丝氨酸蛋白酶抑制剂肽酶抑制剂 E 族成员 2 (SERPINE2) 与肿瘤转移密切相关。本研究旨在探讨 SERPINE2 是否与表皮生长因子 (EGF)/表皮生长因子受体 (EGFR) 形成反馈回路,从而调节人甲状腺乳头状癌细胞 (TPC-1) 的细胞过程。采用逆转录-定量 PCR 和 Western blot 分析 SERPINE2 的表达。使用细胞增殖和细胞毒性检测试剂盒 (MTT) 和集落形成实验检测细胞增殖能力。还研究了增殖标志物,包括增殖细胞核抗原和 Ki-67,以分析 TPC-1 细胞的增殖活性。此外,通过划痕愈合和 Transwell 实验分别分析细胞迁移和侵袭,通过 TUNEL 染色分析细胞凋亡。结果表明,SERPINE2 在 TPC 细胞中的表达增加,SERPINE2 和 EGF/EGFR 相互调节。此外,SERPINE2 的过表达和沉默调节了 TPC 细胞的增殖、迁移、侵袭和凋亡。此外,EGFR 抑制剂阻断了 SERPINE2 过表达对上述生物学过程的影响。因此,本研究证实 SERPINE2 与 EGF/EGFR 形成正反馈,调节 TPC 细胞的增殖、侵袭和迁移,可能为甲状腺乳头状癌的潜在治疗靶点提供新的见解。

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