Abstract
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.