IL-17C对口腔鳞状细胞癌的保护作用。

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2025-09-19 DOI:10.1016/j.tranon.2025.102541

Zivile Giedraityte , Joosua Suominen , Wafa Wahbi , Ahana Kapuge Dona Varuni Yashodha Ratnayake , Tuulia Onali , Martina Giacomini , Sami Kilpinen , Katja Korelin , Maija Risteli , Tuula Salo , Ahmed Al-Samadi

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引用次数: 0

摘要

背景：口腔鳞状细胞癌（OSCC）是一种常见的癌症，具有高转移率和高死亡率。白细胞介素-17C （IL-17C）由多种细胞类型表达，包括上皮细胞，并通过不同粘膜部位的异二聚体IL-17RE/IL-17RA受体复合物发出信号。IL-17C在OSCC发生和进展中的作用尚未得到研究；因此，本研究旨在阐明其潜在的参与。方法：选取11株OSCC细胞系中IL-17C受体（IL-17RE和IL-17RA）高转录表达的OU-OTSCC-7B和UH-SCC-17B进行进一步检测。在IL-17C存在和不存在的情况下进行增殖、凋亡、迁移和侵袭试验。利用斑马鱼异种移植模型，我们评估了IL-17C在体内的作用。此外，我们用IL-17C刺激UH-SCC-17B细胞后进行RNA测序。结果：IL-17C显著抑制UH-SCC-17B细胞的增殖和迁移，而对OU-OTSCC-7B细胞无影响。此外，IL-17C在斑马鱼模型中使UH-SCC-17B细胞的肿瘤大小减少了约10%。RNA测序揭示了5个基因的下调，其中3个是线粒体基因- mt - cyb， MT-ND1和mtnd2p28 -与癌症进展有关。基因集富集分析显示，IL-17C处理后MYC靶基因和氧化磷酸化基因集富集。结论：IL-17C在部分OSCC细胞中发挥保护作用。虽然本研究表明IL-17C有可能作为OSCC患者的候选治疗药物，但其相对温和的选择性作用表明，作为联合治疗的一部分，IL-17C可能更有效。

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The protective role of IL-17C in oral squamous cell carcinoma

Background

Oral squamous cell carcinoma (OSCC) is a common cancer characterised by high rates of metastasis and mortality. Interleukin‑17C (IL-17C) is expressed by several cell types, including epithelial cells, and signals through the heterodimeric IL-17RE/IL-17RA receptor complex at various mucosal sites. The role of IL-17C in OSCC development and progression remains unexamined; therefore, this study aimed to elucidate its potential involvement.

Methods

Among 11 OSCC cell lines, OU-OTSCC-7B and UH-SCC-17B exhibited a high transcript expression of IL-17C receptors (IL-17RE and IL-17RA) and were selected for further assays. Proliferation, apoptosis, migration, and invasion assays were conducted in the presence and absence of IL-17C. Using a zebrafish xenograft model, we assessed the in vivo effects of IL-17C. Additionally, we performed RNA sequencing after stimulating UH-SCC-17B cells with IL-17C.

Results

IL-17C significantly inhibited the proliferation and migration of UH-SCC-17B cells, but had no effect on OU-OTSCC-7B cells. Moreover, IL-17C reduced the tumour size of UH-SCC-17B cells by approximately 10% in the zebrafish model. RNA sequencing revealed the downregulation of five genes, three of which were mitochondrial genes—MT-CYB, MT-ND1, and MTND2P28—implicated in cancer progression. Gene set enrichment analysis revealed the enrichment of the MYC target and oxidative phosphorylation gene sets following IL-17C treatment.

Conclusions

IL-17C appears to play a protective role in some OSCC cells. While this study indicates the potential of using IL-17C as a therapeutic candidate for OSCC patients, its relatively mild and selective effect suggests it may be more effective as part of a combination therapy.

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.