Surgical Oncology, Hangzhou Cancer Hospital, Hangzhou City, Zhejiang Province, China.
Department of Nuclear Medicine, Hangzhou Cancer Hospital, Hangzhou City, Zhejiang Province, China.
Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820983290. doi: 10.1177/1533033820983290.
The annual incidence of papillary thyroid carcinoma has increased dramatically. T cell factor 4 (TCF4) is an important component of Wnt signaling pathway.However, the role of TCF4 in PTC remains unknown. In this study, TCF4 was observed to overexpress in PTC patients and cells by qRT-PCR assay. The colony formation assay, Edu staining and transwell assay indicated thatoverexpression of TCF4 promoted cell proliferation and invasion of TCP-1 cells, whereas knockdown of TCF4 inhibited cell proliferation and invasion of IHH-4 cells. To investigate the mechanism of TCF4 in PTC cells, the luciferase assay demonstrated that TCF4 could modulate HCP5 expression. Besides, GLuc-ON promoter reporter assayproved that TCF4 could bind to HCP5 promoter. Further, knockdown of HCP5 could significantly up-regulated miR-15a, miR-216a-5p, miR-22-3p, miR-139-5p, miR-203, miR-27a-3p and miR-320, and down-regulated miR-186-5p in IHH-4 cells, which might be potential downstream of TFC4/HCP5 axis. In conclusion, up-regulation TCF4 can promote HCP5 expression via binding to HCP5 promoter. It may be the first time to prove that TCF4 regulates HCP5 in PTC, which provides a novel sight for treatment of PTC.
甲状腺乳头状癌的年发病率显著增加。T 细胞因子 4(TCF4)是 Wnt 信号通路的重要组成部分。然而,TCF4 在 PTC 中的作用尚不清楚。在这项研究中,通过 qRT-PCR 检测发现 TCF4 在 PTC 患者和细胞中过表达。集落形成实验、Edu 染色和 Transwell 实验表明,TCF4 的过表达促进了 TCP-1 细胞的增殖和侵袭,而 TCF4 的敲低则抑制了 IHH-4 细胞的增殖和侵袭。为了研究 TCF4 在 PTC 细胞中的作用机制,荧光素酶报告基因实验表明 TCF4 可以调节 HCP5 的表达。此外,GLuc-ON 启动子报告基因实验证明 TCF4 可以结合 HCP5 启动子。进一步研究发现,敲低 HCP5 可以显著上调 IHH-4 细胞中的 miR-15a、miR-216a-5p、miR-22-3p、miR-139-5p、miR-203、miR-27a-3p 和 miR-320,同时下调 miR-186-5p,这可能是 TCF4/HCP5 轴的潜在下游靶点。综上所述,上调 TCF4 可以通过结合 HCP5 启动子促进 HCP5 的表达。这可能是首次证明 TCF4 在 PTC 中调节 HCP5,为 PTC 的治疗提供了新的思路。