Identification of novel molecules and pathways associated with fascin actin‑bundling protein 1 in laryngeal squamous cell carcinoma through comprehensive transcriptome analysis

Int J Mol Med. 2024 Apr;53(4):39. doi: 10.3892/ijmm.2024.5363. Epub 2024 Mar 1.

Abstract

Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor with a poor prognosis. Fascin actin‑bundling protein 1 (FSCN1) has been reported to play a crucial role in the development and progression of LSCC; however, the underlying molecular mechanisms remain unknown. Herein, a whole transcriptome microarray analysis was performed to screen for differentially expressed genes (DEGs) in cells in which FSCN1 was knocked down. A total of 462 up and 601 downregulated mRNA transcripts were identified. Functional annotation analysis revealed that these DEGs were involved in multiple biological functions, such as transcriptional regulation, response to radiation, focal adhesion, extracellular matrix‑receptor interaction, steroid biosynthesis and others. Through co‑expression and protein‑protein interaction analysis, FSCN1 was linked to novel functions, including defense response to virus and steroid biosynthesis. Furthermore, crosstalk analysis with FSCN1‑interacting proteins revealed seven DEGs, identified as FSCN1‑interacting partners, in LSCC cells, three of which were selected for further validation. Co‑immunoprecipitation validation confirmed that FSCN1 interacted with prostaglandin reductase 1 and 24‑dehydrocholesterol reductase (DHCR24). Of note, DHCR24 is a key enzyme involved in cholesterol biosynthesis, and its overexpression promotes the proliferation and migration of LSCC cells. These findings suggest that DHCR24 is a novel molecule associated with FSCN1 in LSCC, and that the FSCN1‑DHCR24 interaction may promote LSCC progression by regulating cholesterol metabolism‑related signaling pathways.

Keywords: 24‑dehydrocholesterol reductase; cholesterol metabolism; co‑expression; fascin; laryngeal squamous cell carcinoma; protein‑protein interaction.

MeSH terms

  • Actins / metabolism
  • Carcinoma, Squamous Cell* / metabolism
  • Carrier Proteins*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cholesterol
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms* / genetics
  • Humans
  • Laryngeal Neoplasms* / metabolism
  • MicroRNAs* / genetics
  • Microfilament Proteins*
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Steroids

Substances

  • fascin
  • Actins
  • Cholesterol
  • Oxidoreductases
  • Steroids
  • MicroRNAs
  • FSCN1 protein, human
  • Carrier Proteins
  • Microfilament Proteins

Grants and funding

The present study was supported by the National Natural Science Foundation of China (grant no. 81802793), the Basic Research Program of Shanxi Province (Free Exploration) (grant nos. 202203021211015, 20210302124704, 20210302124594 and 202103021223430), the Science Research Start-up Fund for Doctor of Shanxi Medical University (XD1801), Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi (STIP; grants 2021-185), and the Medical Science and Technology Innovation Team of Shanxi Province (grant no. 2020TD26).