Abstract
Background Cytokines play important roles in the development and prognosis of laryngeal cancer (LC). Interleukin-17 (IL-17) from a distinct subset of CD4+ T cells may significantly induce cancer-elicited inflammation to prevent tumor immune surveillance. Methods The expression levels of IL-17 were examined among 60 patients with LC. Immunofluorescence colocalization experiments were performed to verify the localization of IL-17 and FAS/FASL in Hep-2 and Tu212 cells. The role of IL-17 was determined using siRNA techniques in the LC cell line. Results In the LC patients, cytokines were dysregulated in LC tissues compared with normal tissues. It was found that IL-17 was overexpressed in a cohort of 60 LC tumors paired with nontumor tissues. Moreover, high IL-17 expression was significantly associated with the advanced T category, the late clinical stage, differentiation, lymph node metastasis, and recurrence. In addition, the time course expression of FAS and FASL was observed after stimulation and treatment with the IL-17 stimulator. Finally, in vitro experiments demonstrated that IL-17 functioned as an oncogene by inhibiting the apoptosis of LC cells via the PI3K/AKT/FAS/FASL pathways. Conclusions In summary, these findings demonstrated for the first time the role of IL-17 as a tumor promoter and a prometastatic factor in LC and indicated that IL-17 may have an oncogenic role and serve as a potential prognostic biomarker and therapeutic target in LC.
Highlights
Cytokines play important roles in the development and prognosis of laryngeal cancer (LC)
The Western blotting in the different pathological grades of LC tissues showed that the expression levels of the IL-17 and IL-17R proteins increased significantly with increasing severity of LC. These findings were consistent with the P-AKT and P-PI3K levels of protein expression, while the expression of FAS and FASL in the LC tissues decreased significantly
These results indicated that the silencing of IL-17 expression mediated apoptosis via the PI3K/AKT/FAS/FASL pathways in LC cells
Summary
Cytokines play important roles in the development and prognosis of laryngeal cancer (LC). In vitro experiments demonstrated that IL-17 functioned as an oncogene by inhibiting the apoptosis of LC cells via the PI3K/AKT/FAS/FASL pathways. These findings demonstrated for the first time the role of IL-17 as a tumor promoter and a prometastatic factor in LC and indicated that IL-17 may have an oncogenic role and serve as a potential prognostic biomarker and therapeutic target in LC. The development of laryngeal carcinoma (LC) has increased recently and is the second most common malignant tumor of the head and neck. It is the sixth most common tumor worldwide, with a five-year survival rate of approximately 50% [1]. T helper cell 17secreting cells (Th17) are the primary source of IL-17, while other cell types develop this cytokine, such as group 3 innate lymphoid cells (ILC3), δγT cells, and natural killer
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