The role of the circ_DOCK1-miR-1297-HOXA9 regulatory network in the development of oral squamous cell carcinoma

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice Pub Date : 2025-02-01 DOI:10.1016/j.prp.2024.155752

Bingxin Mei, Zhimei Zeng, Qinmin Xia, Ming Liu, Ying Zhang

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引用次数: 0

Abstract

Objective

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.

Methods

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.

Results

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.

Conclusion

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.

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circ_DOCK1-miR-1297-HOXA9调控网络在口腔鳞状细胞癌发展中的作用

目的：口腔鳞状细胞癌（OSCC）是一个公共卫生问题。本研究旨在探讨circRNA细胞分裂献身者1 （circ_DOCK1）在OSCC中的作用及其相关的作用模式。方法：采用实时荧光定量聚合酶链式反应（qRT-PCR）检测circ_DOCK1和microRNA-1297 （miR-1297）的表达。应用EdU法、菌落形成法、transwell法和糖酵解应激试验进行功能分析。western blot检测homobox A9 （HOXA9）表达水平。通过双荧光素酶报告基因实验验证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。结果：Circ_DOCK1在OSCC肿瘤组织和细胞系中高表达。Circ_DOCK1敲低可抑制OSCC细胞的集落形成、迁移、侵袭和糖酵解。MiR-1297被circ_DOCK1靶向，其抑制逆转了circ_DOCK1敲低的抗癌作用。HOXA9是miR-1297的靶点，其过表达恢复了miR-1297再引入引起的OSCC细胞中集落形成、迁移、侵袭和糖酵解的抑制。此外，circ_DOCK1敲低在体内抑制肿瘤生长。结论：Circ_DOCK1部分通过Circ_DOCK1 - mir -1297- hoxa9调控网络发挥其在OSCC中的致癌作用，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希望的生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pathology, research and practice 医学-病理学

CiteScore

5.00

自引率

3.60%

发文量

405

审稿时长

24 days

期刊介绍： Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.