Upregulation of SQLE Contributes to Poor Survival in Head and Neck Squamous Cell Carcinoma

Int J Biol Sci. 2022 May 16;18(9):3576-3591. doi: 10.7150/ijbs.68216. eCollection 2022.

Abstract

Recently, increasing attention has been paid to the role of Squalene epoxidase (SQLE) in several types of cancers. However, its functional role in tumor progression of head and neck squamous cell carcinoma (HNSCC) is still unclear. We performed bioinformatic analyses and relative experiments to assess the potential mechanism of SQLE-mediated HNSCC malignancy. And the results showed that SQLE was significantly upregulated in tumor samples compared with peritumor samples. Mechanistically, miR-584-5p downregulation may lead to the upregulation of SQLE in HNSCC. Moreover, high SQLE expression in HNSCC was associated with TNM stage, distant metastasis, and poor survival, indicating that SQLE be involved in the progression of HNSCC. Furtherly, SQLE boosted proliferation, migration, invasion of HNSCC cells in vitro and in vivo. Bioinformatic studies showed that PI3K/Akt signaling participated in HNSCC progression mediated by SQLE overexpression, which is confirmed by in vitro and in vivo analysis. Particularly, treatment with terbinafine, an inhibitor of SQLE widely used in the treatment of fungal infections, showed a therapeutic influence on HNSCC. Our findings demonstrate that SQLE plays a vital role in HNSCC progression, providing research evidence for SQLE as a prospective HNSCC therapeutic target and for terbinafine as a candidate drug of HNSCC treatment in the future.

Keywords: HNSCC; SQLE; prognosis; terbinafine; tumor progression.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Head and Neck Neoplasms* / genetics
  • Humans
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Prospective Studies
  • Squalene Monooxygenase* / genetics
  • Squalene Monooxygenase* / metabolism
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Terbinafine
  • Up-Regulation / genetics

Substances

  • Squalene Monooxygenase
  • Terbinafine