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

IF 2.3 4区医学 Q3 ONCOLOGY

Current cancer drug targets Pub Date : 2024-01-01 DOI:10.2174/0115680096294098240123104657

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

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引用次数: 0

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.

Objectives: 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 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 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).

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

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PPT1 促进口腔鳞状细胞癌细胞的生长并抑制其铁蛋白沉积。

背景：口腔鳞状细胞癌（OSCC口腔鳞状细胞癌（OSCC）是头颈部最常见的癌症之一，预后较差。阐明 OSCC 发生和发展的分子机制对治疗非常重要。棕榈酰化相关酶的失调在多种癌症中均有报道，但 OSCC 除外：探讨棕榈酰蛋白硫酯酶 1（PPT1）在 OSCC 中的作用：方法：通过不同的在线数据库筛选并构建正常口腔上皮组织和OSCC组织之间的差异表达基因（DEGs）和相关蛋白-蛋白相互作用网络。对 70 例 OSCC 患者的肿瘤样本进行了评估，以确定 PPT1 表达水平与患者临床特征之间的关系。PPT1在OSCC增殖和转移中的作用通过功能实验进行了研究，包括MTT、菌落形成、EdU掺入和透孔实验。研究使用基于慢病毒的构建体来操纵基因表达。利用铁橙探针和丙二醛检测法确定铁变态反应。通过异种移植小鼠模型研究了 OSCC 细胞在体内的生长情况：结果：共获得 555 个 DEGs，拓扑分析表明 PPT1 和 GPX4 可能在 OSCC 中发挥关键作用。PPT1表达的增加与OSCC患者的不良预后相关。PPT1能有效促进OSCC细胞的增殖、迁移和侵袭，同时抑制OSCC细胞的铁变态反应。PPT1影响谷胱甘肽过氧化物酶4（GPX4）的表达：结论：PPT1能促进OSCC细胞的生长并抑制其铁细胞凋亡。结论：PPT1能促进OSCC细胞的生长并抑制其铁细胞凋亡，可能是OSCC治疗的潜在靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current cancer drug targets 医学-肿瘤学

CiteScore

5.40

自引率

0.00%

发文量

105

审稿时长

1 months

期刊介绍： Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes. Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer. As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.