| Objective:Our preliminary clinical study suggested that the expression of Interleukin (IL)-11 is positively associated with distant metastasis and negatively associated with poor prognosis in patients with anaplatic thyroid carcinoma (ATC). This study aims to explore the role of IL-11 on promoting ATC cells invasion and metastasis and clarify its mechanism.Methods:Real-time PCR was performed for examming the IL-11 mRNA expression in thyroid carcinoma cell lines, and IL-11 protein expression in the supernament of thyroid carcinoma cell lines were measured by ELISA. Molecular cloning was employed to construct the IL-11-shRNA eukaryotic expression vector:pSUPER-shIL-11 and IL-11 stable knockdown cell line; Treat ATC cell lines with cobalt chloride which simulated hypoxia. ELISA and Real-time PCR were performed for examming the expression of IL-11 protein and mRNA in stable cell lines; Transwell and wound healing assays were employed to analyze the abilities of migration and invasion of ATC cells. Western blot was used to examine the relative pathway proteins.Results:IL-11-shRNA eukaryotic expression vector:pSUPER-shIL-11 and IL-11 stable knockdown cell lines were constructed successfully. The expression of IL-11 protein and mRNA in IL-11 stable cell lines was significantly down-regulated compared with the control group. Transwell invasion and migration assays and wound healing assays confirmed that IL-11 or cobalt chloride could upregulate the migratory and invasive abilities via induce epithelial-mesenchymal transition(EMT), followed with the change of relative pathway proteins.Conclusion:We demonstrated that cobalt chloride (CoCl2, a hypoxia mimetic), induces HIF-la and promotes the expression of IL-11. Then, IL-11 induces the EMT in ATC cells via the PI3K/Akt/GSK3p signaling pathway and ultimately promotes the invasive and migratory abilities of ATC cells. This discovery could lead to the development of prognostic or predictive tools as well as the identification of possible drug targets. |
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