Interleukin-17A Promotes Tongue Squamous Cell Carcinoma Metastasis Through miR-23b/versican Pathway

Objectives: Interleukin-17A (IL-17A), a proinflammatory cytokine mainly produced by Th17 cells, exerts protumor or antitumor effects in different cancer entities. However, the exact role of IL-17A in carcinogenesis and progression of cancer remains unclear.
Methods: Serum cytokines levels were analyzed by enzyme linked immunosorbent assay. Both quantitative real-time PCR and immunohistochemistry were used to detect IL-17A expression. Identification of the biological functions of IL-17A and associated mechanisms was accomplished by use of SCC15 cells.
Results: The levels of IL-17A in serum and tumor samples were significantly increased in tongue squamous cell carcinoma (TSCC) patients and positively correlated with tumor metastasis and clinical stage. Besides, treatment of TSCC cell line SCC15 with IL-17A enhanced cell migration and invasion. Furthermore, IL-17A inversely correlated with miR-23b expression in TSCC specimens and IL-17A downregulated miR-23b expression via activating NF-κB in SCC15 cells. Overexpression of miR-23b inhibited, whereas knockdown of miR-23b promoted migration and invasion abilities of SCC15 cells. Moreover, extracellular matrix protein versican was proved to be the direct target of miR-23b. IL-17A increased versican levels in vitro and knockdown of versican by siRNA inhibited SCC15 cell migration and invasion.
Conclusions: These results reveal a novel mechanism that IL-17A in TSCC microenvironment promotes the migration and invasion of TSCC cells through targeting miR-23b/versican pathway.