MiR-32-5p promoted epithelial-to-mesenchymal transition of oral squamous cell carcinoma cells via regulating the KLF2/CXCR4 pathway

Kaohsiung J Med Sci. 2022 Feb;38(2):120-128. doi: 10.1002/kjm2.12450. Epub 2021 Nov 6.

Abstract

Oral squamous cell carcinoma (OSCC) is one of the most common carcinomas of the oral cavity. However, the regulatory mechanisms on miR-32-5p remain poorly understood in OSCC. The expression of miR-32-5p, Krüppel-like factor 2 (KLF2), C-X-C motif chemokine receptor 4 (CXCR4), and epithelial-to-mesenchymal transition (EMT)-related proteins (E-cadherin, Vimentin, N-cadherin, and Snail) were evaluated were assessed using RT-qPCR and Western blot. 3-(4, 5-Dimethylthiazolyl2)-2, 5-diphenyltetrazolium bromide assay, wound healing assay, and transwell assay were employed to detect cell proliferation, migration, and invasion of OSCC cells. Finally, dual-luciferase reporter assay was performed to verify the binding relationship between KLF2 and miR-32-5p. MiR-32-5p was highly expressed while KLF2 was lowly expressed in OSCC cells, and miR-32-5p knockdown or KLF2 overexpression could markedly reduce cell proliferation, migration, invasion, and EMT of OSCC cells. What is more, KLF2 was the target of miR-32-5p, and knockdown of KLF2 abolished the inhibitory effect of miR-32-5p inhibitor on progression of OSCC. Finally, CXCR4 expression was negatively regulated by KLF2, and inhibition of CXCR4 obviously alleviated the biological effects of si-KLF2 on the progression of OSCC. MiR-32-5p could enhance cell proliferation, migration, invasion, and EMT of OSCC cells, and the discovery of miR-32-5p/KLF2/CXCR4 axis might provide potential therapeutic targets for OSCC.

Keywords: CXCR4; EMT; KLF2; miR-32-5p; oral squamous cell carcinoma.

MeSH terms

  • Carcinoma, Squamous Cell / pathology*
  • Epithelial-Mesenchymal Transition*
  • Humans
  • Kruppel-Like Transcription Factors / physiology*
  • MicroRNAs / physiology*
  • Mouth Neoplasms / pathology*
  • Receptors, CXCR4 / physiology*
  • Signal Transduction
  • Tumor Cells, Cultured

Substances

  • CXCR4 protein, human
  • KLF2 protein, human
  • Kruppel-Like Transcription Factors
  • MIRN32 microRNA, human
  • MicroRNAs
  • Receptors, CXCR4