LncRNA FEZF1-AS1 accelerates the migration and invasion of laryngeal squamous cell carcinoma cells through miR-4497 targeting GBX2

Eur Arch Otorhinolaryngol. 2021 May;278(5):1523-1535. doi: 10.1007/s00405-021-06636-5. Epub 2021 Feb 7.

Abstract

Background: MiR-4497 has been previously proved to exert an anti-cancer role in laryngeal squamous cell carcinoma (LSCC) by negatively regulating gastrulation brain homeobox 2 (GBX2). However, the mechanism of miR-4497 in LSCC has yet to be fully elucidated. This study intended to investigate the role of FEZF1-AS1 in the migration and invasion of LSCC cells and clarified its mechanism through miR-4497 and GBX2.

Methods: qPCR evaluated the expression of FEZF1-AS1, miR-4497 and GBX2 in LSCC tissues and cells, compared with controls. Western blotting analyzed GBX2, E-cadherin, N-cadherin and Vimentin. CCK8, wound healing and transwell assays assessed the viability, migration and invasion of TU686 and UM-SCC-17A cells. Luciferase reporter assay affirmed the interplay of miR-4497 with FEZF1-AS1 or GBX2 and Pearson's correlation analysis explored the association between each two genes in both tumor and non-tumor tissues.

Results: FEZF1-AS1 was highly expressed in LSCC tissues and cells. Silence or elevation of FEZF1-AS1 inhibited or promoted the migration and invasion of TU686 and UM-SCC-17A cells. FEZF1-AS1 targeted and negatively modulated miR-4497. Inhibition of miR-4497 markedly restored the FEZF1-AS1 silence-repressed cell viability of TU686 and UM-SCC-17A cells. Further, FEZF1-AS1 could positively regulate GBX2 via negative regulation of miR-4497. In these two cells, GBX2 deficiency reversed the promoting impacts of miR-4497 repression on migration and invasion.

Conclusion: Taken together, FEZF1-AS1, heightened in LSCC tissues and cells, promotes cell migration and invasion of LSCC cells via targeting miR-4497 that inhibits GBX2. The finding may offer new options for the treatment of this cancer.

Keywords: FEZF1-AS1; GBX2; Invasion; Laryngeal squamous cell carcinoma; Migration; miR-4497.

MeSH terms

  • Cell Proliferation
  • Head and Neck Neoplasms*
  • Homeodomain Proteins
  • Humans
  • MicroRNAs* / genetics
  • RNA, Long Noncoding*
  • Squamous Cell Carcinoma of Head and Neck / genetics

Substances

  • GBX2 protein, human
  • Homeodomain Proteins
  • MIRN4497 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding