circBICD2 targets miR-149-5p/IGF2BP1 axis to regulate oral squamous cell carcinoma progression

J Oral Pathol Med. 2021 Aug;50(7):668-680. doi: 10.1111/jop.13156. Epub 2021 Feb 2.

Abstract

Background: Circular RNAs (circRNAs) are related to oral squamous cell carcinoma (OSCC) progression. circRNA bicaudal D cargo adaptor 2 (circBICD2) has been reported to be abnormally expressed in OSCC. However, the function and mechanism of this circRNA in OSCC progression remain largely unknown.

Methods: circBICD2, microRNA-149-5p (miR-149-5p), and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) abundances were examined via quantitative reverse transcription polymerase chain reaction or Western blot. The function of circBICD2 was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, flow cytometry, wound healing, transwell, specific kits, Western blot, and xenograft analyses. Dual-luciferase reporter analysis and RNA immunoprecipitation were carried out to analyze the binding interaction.

Results: circBICD2 expression was enhanced in OSCC tissues and cells. circBICD2 silence suppressed OSCC cell proliferation, migration, invasion, and glutaminolysis and facilitated apoptosis. miR-149-5p was targeted via circBICD2 and decreased in OSCC tissues and cells. miR-149-5p knockdown attenuated silence of circBICD2 on the influence of OSCC cell proliferation, apoptosis, migration, invasion, and glutaminolysis. IGF2BP1 was targeted via miR-149-5p, and circBICD2 could regulate IGF2BP1 via miR-149-5p. IGF2BP1 interference constrained OSCC cell proliferation, migration, invasion, and glutaminolysis and promoted apoptosis. circBICD2 silence reduced OSCC cell growth in xenograft model.

Conclusion: circBICD2 knockdown repressed OSCC cell proliferation, migration, invasion, and glutaminolysis and increased apoptosis via modulating miR-149-5p/IGF2BP1 axis, which might act as a potential target for OSCC treatment.

Keywords: IGF2BP1; circBICD2; miR-149-5p; oral squamous cell carcinoma.

MeSH terms

  • Carcinoma, Squamous Cell* / genetics
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Head and Neck Neoplasms*
  • Humans
  • MicroRNAs* / genetics
  • Microtubule-Associated Proteins
  • Mouth Neoplasms* / genetics
  • RNA, Circular* / genetics
  • RNA-Binding Proteins* / genetics
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • BICD2 protein, human
  • IGF2BP1 protein, human
  • MIRN149 microRNA, human
  • MicroRNAs
  • Microtubule-Associated Proteins
  • RNA, Circular
  • RNA-Binding Proteins