School of Medicine, Yunnan University, Kunming, China.
Department of Prosthodontics of Kunming Medical University, Stomatology Hospital of Kunming Medical University, Kunming, China.
Oral Dis. 2024 Apr;30(3):977-990. doi: 10.1111/odi.14527. Epub 2023 Mar 29.
The aim of this study was to investigate the molecular mechanism by which the transcription factor ETS1 regulates N-myc downstream regulatory gene 1 (NDRG1) to provide a new theoretical basis for the study of oral squamous cell carcinoma (OSCC).
In this study, eight human OSCC and paraneoplastic samples were collected. The expressions of NDRG1, ETS1, and Ki67 were detected by immunohistochemistry; apoptosis was detected by tdt-mediated dUTP notched end labeling; cell migration and invasion were detected by Transwell; quantitative real-time PCR was performed to detect the expression of NDRG1; RNA-binding protein immunoprecipitation (RIP) assays detected NDRG1 expression; immunofluorescence assays detected ETS1 expression.
NDRG1 and ETS1 expression was significantly upregulated in cancer tissues and CAL-27 and SCC-6 cells. Knockdown of NDRG1 and ETS1 inhibited cell proliferation, migration, invasion, cloning, and EMT while promoting apoptosis and inhibited tumor development; ETS1 positively regulated NDRG1 expression; Finally, overexpression of NDRG1 in vivo and in vitro reversed the effect of ETS1 knockdown on CAL-27 and SCC-6 cells.
ETS1 positively regulates the expression of NDRG1 and promotes OSCC. Therefore, ETS1 may serve as a new target for the clinical diagnosis and treatment of OSCC.
本研究旨在探讨转录因子 ETS1 调节 N-myc 下游调节基因 1（NDRG1）的分子机制，为口腔鳞状细胞癌（OSCC）的研究提供新的理论依据。
本研究收集了 8 例人 OSCC 及癌旁组织标本。采用免疫组化法检测 NDRG1、ETS1 和 Ki67 的表达；采用 TUNEL 法检测细胞凋亡；Transwell 法检测细胞迁移和侵袭；实时定量 PCR 检测 NDRG1 的表达；RNA 结合蛋白免疫沉淀（RIP）实验检测 NDRG1 的表达；免疫荧光法检测 ETS1 的表达。
NDRG1 和 ETS1 在癌组织和 CAL-27 及 SCC-6 细胞中表达明显上调。敲低 NDRG1 和 ETS1 抑制细胞增殖、迁移、侵袭、克隆形成和 EMT，促进细胞凋亡，抑制肿瘤发展；ETS1 正向调控 NDRG1 的表达；最后，体内和体外过表达 NDRG1 逆转了 ETS1 敲低对 CAL-27 和 SCC-6 细胞的作用。
ETS1 正向调节 NDRG1 的表达，促进 OSCC 的发生。因此，ETS1 可能成为 OSCC 临床诊断和治疗的新靶点。
