WDR5 promotes the tumorigenesis of oral squamous cell carcinoma via CARM1/β-catenin axis

Odontology. 2022 Jan;110(1):138-147. doi: 10.1007/s10266-021-00649-6. Epub 2021 Aug 16.

Abstract

Oral squamous cell carcinoma (OSCC) is a malignancy all over the world. WD repeat domain 5 (WDR5) is involved in cancer progression. In addition, it was reported that WDR5 is upregulated in head and neck cancer, while its role in OSCC is unknown. First, the expression of WDR5 in oral cancer tissues and cells was examined by qRT-PCR, IHF and western blot. CCK-8 assay was performed to test the cell viability. Cell migration was assessed by transwell assay. Knocking down WDR5 or CARM1 in oral cancer cells to detect its function on cancer growth, WDR5 and CARM1 were significantly upregulated in OSCC. Silencing WDR5 suppressed OSCC cell viability and migration. CARM1 level in OSCC cells was significantly inhibited by WDR5 downregulation, and CARM1 elevation could rescue the effect of WDR5 knockdown on tumorigenesis of OSCC. Moreover, silencing of WDR5 notably inactivated β-catenin signaling pathway, while this phenomenon was restored by CARM1 overexpression. Silencing of WDR5 attenuated the tumorigenesis of OSCC via CARM1/β-catenin axis. Thus, WDR5 might be a target for OSCC treatment.

Keywords: CARM1; OSCC; Oral cancer; WDR5; β-catenin.

MeSH terms

  • CARD Signaling Adaptor Proteins
  • Carcinogenesis / genetics
  • Carcinoma, Squamous Cell* / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Guanylate Cyclase
  • Head and Neck Neoplasms*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Mouth Neoplasms* / genetics
  • Protein-Arginine N-Methyltransferases
  • Signal Transduction
  • Squamous Cell Carcinoma of Head and Neck
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • CARD Signaling Adaptor Proteins
  • CTNNB1 protein, human
  • Intracellular Signaling Peptides and Proteins
  • WDR5 protein, human
  • beta Catenin
  • Protein-Arginine N-Methyltransferases
  • coactivator-associated arginine methyltransferase 1
  • CARD11 protein, human
  • Guanylate Cyclase