Mei Bingxin, Zeng Zhimei, Xia Qinmin, Liu Ming, Zhang Ying
Department of Stomatology, The First Affiliated Hospital Of Gannan Medical University, Ganzhou, China.
Department of Stomatology, The First Affiliated Hospital Of Gannan Medical University, Ganzhou, China.
Pathol Res Pract. 2025 Feb;266:155752. doi: 10.1016/j.prp.2024.155752. Epub 2024 Dec 16.
Oral squamous cell carcinoma (OSCC) is a public health concern. The current study aimed to explore the role of circRNA Dedicator of Cytokinesis 1 (circ_DOCK1) and associated action mode in OSCC.
The expression of circ_DOCK1 and microRNA-1297 (miR-1297) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). EdU assay, colony formation assay, transwell assay and glycolysis stress test were applied for functional analyses. The expression level of Homeobox A9 (HOXA9) was detected by western blot. The interaction between miR-1297 and circ_DOCK1 or HOXA9 was verified by dual-luciferase reporter assay. Xenograft model was established to determine the role of circ_DOCK1 in vivo.
Circ_DOCK1 was highly expressed in OSCC tumor tissues and cell lines. Circ_DOCK1 knockdown suppressed colony formation, migration, invasion and glycolysis of OSCC cells. MiR-1297 was targeted by circ_DOCK1, and its inhibition reversed the anticancer effects of circ_DOCK1 knockdown. HOXA9 was a target of miR-1297, and its overexpression recovered miR-1297 reintroduction-evoked inhibition of colony formation, migration, invasion and glycolysis in OSCC cells. Furthermore, circ_DOCK1 knockdown repressed tumor growth in vivo.
Circ_DOCK1 exerted its carcinogenic role in OSCC partially via the circ_DOCK1-miR-1297-HOXA9 regulatory network, which will broaden our insights to understand the pathogenesis of OSCC and provide promising biomarkers for the diagnosis and treatment of OSCC.
口腔鳞状细胞癌(OSCC)是一个公共卫生问题。本研究旨在探讨细胞分裂驱动蛋白1环状RNA(circ_DOCK1)在OSCC中的作用及相关作用模式。
采用定量实时聚合酶链反应(qRT-PCR)检测circ_DOCK1和微小RNA-1297(miR-1297)的表达。采用EdU检测、集落形成检测、Transwell检测和糖酵解应激试验进行功能分析。通过蛋白质免疫印迹法检测同源盒A9(HOXA9)的表达水平。采用双荧光素酶报告基因检测法验证miR-1297与circ_DOCK1或HOXA9之间的相互作用。建立异种移植模型以确定circ_DOCK1在体内的作用。
Circ_DOCK1在OSCC肿瘤组织和细胞系中高表达。敲低Circ_DOCK1可抑制OSCC细胞的集落形成、迁移、侵袭和糖酵解。miR-1297是circ_DOCK1的靶点,其抑制作用可逆转敲低circ_DOCK1的抗癌作用。HOXA9是miR-1297的靶点,其过表达可恢复miR-1297重新导入所引起的对OSCC细胞集落形成、迁移、侵袭和糖酵解的抑制作用。此外,敲低circ_DOCK1可抑制体内肿瘤生长。
Circ_DOCK1在OSCC中发挥致癌作用部分是通过circ_DOCK1-miR-1297-HOXA9调控网络实现的,这将拓宽我们对OSCC发病机制的认识,并为OSCC的诊断和治疗提供有前景的生物标志物。