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T 细胞因子 4 通过调节长链非编码 RNA HCP5 参与甲状腺乳头状癌的发生。

T Cell Factor 4 Is Involved in Papillary Thyroid Carcinoma via Regulating Long Non-Coding RNA HCP5.

机构信息

Surgical Oncology, Hangzhou Cancer Hospital, Hangzhou City, Zhejiang Province, China.

Department of Nuclear Medicine, Hangzhou Cancer Hospital, Hangzhou City, Zhejiang Province, China.

出版信息

Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820983290. doi: 10.1177/1533033820983290.

Abstract

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.

摘要

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。

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