[SOX2-OT/SOX2 axis regulates lung cancer H520 cell migration via Gli1-mediated epithelial-mesenchymal transition]

Nan Fang Yi Ke Da Xue Xue Bao. 2022 Oct 20;42(10):1431-1439. doi: 10.12122/j.issn.1673-4254.2022.10.01.
[Article in Chinese]

Abstract

Objective: To explore the regulatory role of SOX2-OT in migration of lung squamous cell carcinoma H520 cells and the underlying mechanisms.

Methods: Wound- healing and Transwell migration assays were performed to examine the changes in migration and invasion capacity of lung squamous cell line H520, which expressed higher levels of SOX2-OT than other lung cancer cell lines, following RNA interference-mediated SOX2-OT knockdown. The transcription levels of epithelial-mesenchymal transition (EMT)-related components was detected by qRT-PCR and immunoblotting. Gli1 gain-of-function analysis was performed in H520 cells with SOX2-OT knockdown and the changes in EMT phenotype of the cells were examined. miR-200c mimic and inhibitor were used to analyze the mechanism by which SOX2-OT positively regulates Gli1 and the mediating role of SOX2.

Results: SOX2-OT knockdown significantly lowered the invasiveness and migration capacity of H520 cells and caused changes in EMT phenotype of the cells. Overexpression of Gli1, which was positively regulated by SOX2-OT, reversed the inhibitory effect of SOX2-OT knockdown on migration of H520 cells. Transfection of the cells with miR-200c inhibitor effectively reversed SOX2-OT knockdown-induced down-regulation of SOX2.

Conclusion: The SOX2-OT/SOX2 axis positively regulates migration of lung squamous H520 cells via Gli1-mediated EMT.

Keywords: Gli1; SOX2; SOX2-OT; epithelial-mesenchymal transition; lung squamous cell carcinoma.

Publication types

  • English Abstract

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms* / genetics
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Neoplasm Invasiveness / genetics
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism
  • Zinc Finger Protein GLI1 / genetics
  • Zinc Finger Protein GLI1 / metabolism

Substances

  • Zinc Finger Protein GLI1
  • MicroRNAs
  • GLI1 protein, human
  • SOX2 protein, human
  • SOXB1 Transcription Factors