| Objective:Tristetraprolin (TTP) is a zinc finger RNA-binding protein, which induces the degradation of target mRNAs through binding to the AU-rich elements (AREs) in the 3’-untranslated regions (3’-UTRs). This study aimed to explore the expression, function, and clinical significance of TTP in GC, and to further investigate the regulation of TTP on interleukin 33 (IL-33).Methods:Quantitative Real-time RT-PCR (RT-qPCR) was performed to assess the mRNA level of TTP in GC tissues and cell lines, and immunohistochemistry was performed to detect the protein levels of TTP and IL-33 in GC tissues. Plasmid transfection or RNA interference was used to increase or silence the expression of TTP in GC cells. The changes of TTP and IL-33 expressions were then confirmed by RT-qPCR and Western blotting. Treatment of recombinant human IL-33 was used to study the effect of IL-33 on the function of TTP in GC. CCK-8 assay and trans well assay were performed to evaluate the effects of TTP and IL-33 on the proliferation, migration, and invasion of GC cells in vitro. The role of TTP in regulating tumor growth in vivo was investigated by subcutaneous injection of GC cells in nude mice. At last, statistical analysis was performed in 104 patients with follow-up records over five years to assess the significance of TTP expression in GC diagnosis and prognosis.Results:TTP expression was significantly decreased and inversely correlated with IL-33 expression in GC. TTP could inhibit GC cell proliferation, migration, and invasion through suppression of IL-33. Additionally, reduced TTP expression was associated with depth of invasion, lymph node metastasis, advanced TNM stage, and poor survival of GC patients.Conclusions:TTP is down-regulated and serves as a tumor suppressor in GC. The tumor-suppressive role of TTP may be associated with the regulation of IL-33. TTP is an independent risk factor for poor prognosis of GC patients, and can be used as a potential target for GC treatment. |
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