Dlx5 promotes cancer progression through regulation of CCND1 in oral squamous cell carcinoma (OSCC)

Biochem Cell Biol. 2021 Aug;99(4):424-434. doi: 10.1139/bcb-2020-0523. Epub 2021 Jul 20.

Abstract

Genetic studies have revealed a critical role of the distal-less homeobox gene 5 (Dlx5) in the pathogenesis of ovarian cancer, lung cancer, and T-cell lymphoma; however, the role and underlying mechanisms of Dlx5 in oral squamous cell carcinoma (OSCC) are largely unknown. In this study, we demonstrated that Dlx5 is up-regulated in OSCC tissues and cell lines, compared with their control groups. The results from our immunohistochemistry (IHC) analyses show that high expression levels of Dlx5 correlated with advanced TNM stages (P = 0.0001), lymph node metastasis (P = 0.0049), poor cellular differentiation (P = 0.0491), location of the tumors (P = 0.0132), and poor prognosis for the patient. We also demonstrated that knockdown of Dlx5 inhibited the viability, proliferation, and colony formation of OSCC cell lines CAL-27 and WSU-HN6 cells, probably by blocking cell cycle in the G1 phase. Furthermore, we revealed that Dlx5 exerts its biological functions via direct regulation of CCND1 in CAL-27 and WSU-HN6 cells. Ultimately, we have demonstrated that silencing of Dlx5 inhibits the growth of xenograft tumors in vivo, and that Dlx5 affects the progression of OSCC both in vitro and in vivo via directly regulating CCND1, providing a potential diagnostic biomarker and therapeutic target for OSCC.

Keywords: CCND1; Dlx5; carcinome épidermoïde oral; cell proliferation; oral squamous cell carcinoma; prolifération cellulaire.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Proliferation
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Mice
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology*
  • Prognosis
  • Survival Rate
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • CCND1 protein, human
  • DLX5 protein, human
  • Homeodomain Proteins
  • Transcription Factors
  • Cyclin D1