Knockdown of circGOLPH3 inhibits cell progression and glycolysis by targeting miR-145-5p/lysine demethylase 2A (KDM2A) axis in oral squamous cell carcinoma

Head Neck. 2023 Jan;45(1):225-236. doi: 10.1002/hed.27229. Epub 2022 Oct 21.

Abstract

Background: Oral squamous cell carcinoma (OSCC) is one of the most common head and neck malignancies. The aim of this study is to explore the role of circRNA Golgi phosphoprotein 3 (GOLPH3) (circGOLPH3) in OSCC.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were performed to detect changes in the levels of circGOLPH3, microRNA-145-5p (miR-145-5p), and lysine demethylase 2A (KDM2A). The functions of circGOLPH3 were assessed using in vitro and in vivo assays. Dual-luciferase reporter assay detected the interaction of miR-145-5p with circGOLPH3 or KDM2A.

Results: circGOLPH3 expression was upregulated in OSCC. circGOLPH3 downregulation inhibited cell growth, metastasis, and glycolysis in vitro, and in vivo experiments revealed that circGOLPH3 inhibited tumor growth. In addition, circGOLPH3 bound to miR-145-5p and competitively inhibited KDM2A expression, thereby regulating OSCC cell behaviors as well as glycolysis.

Conclusion: circGOLPH3 exerted pro-oncogenic effects through the miR-145-5p/KDM2A axis to regulate OSCC cell behaviors.

Keywords: KDM2A; OSCC; circGOLPH3; miR-145-5p.

MeSH terms

  • Carcinoma, Squamous Cell* / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation / genetics
  • F-Box Proteins* / genetics
  • F-Box Proteins* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms* / genetics
  • Humans
  • Lysine / genetics
  • Lysine / metabolism
  • Membrane Proteins / genetics
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Mouth Neoplasms* / pathology
  • RNA, Circular / genetics
  • Squamous Cell Carcinoma of Head and Neck / genetics

Substances

  • RNA, Circular
  • Lysine
  • MicroRNAs
  • GOLPH3 protein, human
  • Membrane Proteins
  • KDM2A protein, human
  • F-Box Proteins
  • MIRN145 microRNA, human