Circular hsa_circ_0020377 regulates KLF7 by targeting miR-194-5p to facilitate tumor cell malignant behaviors and glycolysis in oral squamous cell carcinoma progression

Funct Integr Genomics. 2023 Jan 31;23(1):52. doi: 10.1007/s10142-023-00973-w.

Abstract

Oral squamous cell carcinoma (OSCC) is a common malignant tumor with high recurrence, metastasis rates, and poor prognosis. Numerous studies discover that circular RNA (circRNA) is closely associated with OSCC progression. Hsa_circ_0020377 has been aberrantly expressed in OSCC, but its role in tumor growth and metastasis remains largely unclear. Hsa_circ_0020377, microRNA-194-5p (miR-194-5p), and Krüppel-like factor 7 (KLF7) contents were determined by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferative, cycle progression migration, and invasion were measured using 5-ethynyl-2'-deoxyuridine (EdU), Cell Counting Kit-8 (CCK-8), flow cytometry, wound healing, and Transwell assays. The glycolysis level was detected via specific kits. Cyclin D1, E-cadherin, hexokinase 2 (HK2), and KLF7 protein levels were detected via western blot. Using predicting bioinformatics software, the binding between miR-194-5p and hsa_circ_0020377 or KLF7 was verified using a dual-luciferase reporter and RNA Immunoprecipitation (RIP). Beyond that, a xenograft tumor model was used to analyze the role of hsa_circ_0020377 on tumor cell growth in vivo. Increased hsa_circ_0020377 and KLF7 and reduced miR-194-5p were found in OSCC tissues and cell lines. Loss-of-function experiments proved that hsa_circ_0020377 depletion might block OSCC cell proliferation, cycle progression, migration, invasion, and glycolysis in vitro. In xenograft mouse models, hsa_circ_0020377 silencing might suppress tumor growth. In addition, mechanism research suggested that hsa_circ_0020377 could bind with miR-194-5p and enhance its target gene (KLF7), thereby affecting OSCC development. These results broaden our insights regarding the regulation of OSCC progression via circRNA and act as a reference for future clinical studies in OSCC diagnosis and treatment.

Keywords: KLF7; Oral squamous cell carcinoma; hsa_circ_0020377; miR-194-5p.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Kruppel-Like Transcription Factors* / genetics
  • Mice
  • MicroRNAs* / genetics
  • Mouth Neoplasms* / genetics
  • RNA, Circular* / genetics
  • Squamous Cell Carcinoma of Head and Neck* / genetics

Substances

  • KLF7 protein, human
  • Kruppel-Like Transcription Factors
  • MicroRNAs
  • MIRN194 microRNA, human
  • RNA, Circular