PPT1 Promotes Growth and Inhibits Ferroptosis of Oral Squamous Cell Carcinoma Cells

Qingqiong Luo; Sheng Hu; Yijie Tang; Dandan Yang; Qilong Chen

doi:10.2174/0115680096294098240123104657

PPT1 Promotes Growth and Inhibits Ferroptosis of Oral Squamous Cell Carcinoma Cells

Curr Cancer Drug Targets. 2024 Jan 30. doi: 10.2174/0115680096294098240123104657. Online ahead of print.

Authors

Qingqiong Luo^{1

2}, Sheng Hu³, Yijie Tang², Dandan Yang², Qilong Chen^{1

3}

Affiliations

¹ Department of Clinical Immunology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011, Shanghai, China.
² Department of Laboratory Medicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, 200443, Shanghai, China.
³ Central Laboratory, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China.

PMID: 38299399
DOI: 10.2174/0115680096294098240123104657

Abstract

Background: Oral Squamous Cell Carcinoma (OSCC) is one of the most prevalent cancers with poor prognosis in the head and neck. Elucidating molecular mechanisms underlying OSCC occurrence and development is important for the therapy. Dysregulated palmitoylation-related enzymes have been reported in several cancers but OSCC.

Objective: To explore the role of palmitoyl protein thioesterase 1 (PPT1) in OSCC.

Methods: Differentially Expressed Genes (DEGs) and related protein-protein interaction networks between normal oral epithelial and OSCC tissues were screened and constructed via different online databases. Tumor samples from 70 OSCC patients were evaluated for the relationship between PPT1 expression level and patients'clinic characteristics. The role of PPT1 in OSCC proliferation and metastasis was studied by functional experiments, including MTT, colony formation, EdU incorporation and transwell assays. Lentivirus-based constructs were used to manipulate the gene expression. FerroOrange probe and malondialdehyde assay were used to determine ferroptosis. Growth of OSCC cells in vivo was investigated by a xenograft mouse model.

Results: A total of 555 DEGs were obtained, and topological analysis revealed that the PPT1 and GPX4 might play critical roles in OSCC. Increased PPT1 expression was found to be correlated with poor prognosis of OSCC patients. PPT1 effectively promoted the proliferation, migration and invasion while inhibiting the ferroptosis of OSCC cells. PPT1 affected the expression of glutathione peroxidase 4 (GPX4).

Conclusion: PPT1 promoted growth and inhibited ferroptosis of OSCC cells. PPT1 might be a potential target for OSCC therapy.

Keywords: Oral squamous cell carcinoma; differentially expressed genes; ferroptosis.; glutathione peroxidase 4; palmitoyl protein thioesterase 1; proliferation.