Department of Clinical Immunology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011, Shanghai, China.
Department of Laboratory Medicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, 200443, Shanghai, China.
Curr Cancer Drug Targets. 2024;24(10):1047-1060. doi: 10.2174/0115680096294098240123104657.
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.
To explore the role of palmitoyl-protein thioesterase 1 (PPT1) in OSCC.
Differentially expressed genes (DEGs) and related protein-protein interaction networks between normal oral epithelial and OSCC tissues were screened and constructed 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 gene expression. FerroOrange probe and malondialdehyde assay were used to determine ferroptosis. Growth of OSCC cells was investigated by a xenograft mouse model.
A total of 555 DEGs were obtained, and topological analysis revealed that 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 inhibited the ferroptosis of OSCC cells. PPT1 affected the expression of glutathione peroxidase 4 (GPX4).
PPT1 promoted growth and inhibited ferroptosis of OSCC cells. PPT1 might be a potential target for OSCC therapy.
口腔鳞状细胞癌(OSCC)是头颈部最常见的预后不良的癌症之一。阐明 OSCC 发生和发展的分子机制对于治疗具有重要意义。已在几种癌症中报道了失调的棕榈酰化相关酶,但在 OSCC 中没有报道。
探讨棕榈酰蛋白硫酯酶 1(PPT1)在 OSCC 中的作用。
筛选和构建了不同的在线数据库,以获得正常口腔上皮组织和 OSCC 组织之间差异表达的基因(DEGs)和相关的蛋白质-蛋白质相互作用网络。评估了 70 名 OSCC 患者的肿瘤样本,以研究 PPT1 表达水平与患者临床特征之间的关系。通过 MTT、集落形成、EdU 掺入和 Transwell 测定等功能实验研究 PPT1 在 OSCC 增殖和转移中的作用。使用基于慢病毒的构建体来操纵基因表达。使用 FerroOrange 探针和丙二醛测定法来确定铁死亡。通过异种移植小鼠模型研究 OSCC 细胞的生长情况。
获得了总共 555 个 DEGs,拓扑分析表明 PPT1 和 GPX4 可能在 OSCC 中发挥关键作用。发现 PPT1 表达增加与 OSCC 患者的预后不良相关。PPT1 有效地促进了 OSCC 细胞的增殖、迁移和侵袭,同时抑制了铁死亡。PPT1 影响了谷胱甘肽过氧化物酶 4(GPX4)的表达。
PPT1 促进了 OSCC 细胞的生长并抑制了铁死亡。PPT1 可能是 OSCC 治疗的潜在靶点。