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

Pathol Res Pract. 2024 Dec 16:266:155752. doi: 10.1016/j.prp.2024.155752. Online ahead of print.

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.

Keywords: Circ_DOCK1; HOXA9; MiR-1297; OSCC.