Objective:To explore the potential mechanisms of lymphatic metastasis of GC cells regulated by ring finger protein (RNF180).Methods:Associations between clinicopathologic, survival data, and RNF180 expression in GC tissues were analyzed. The effects of RNF180 re-expression and genome microarraywere determined in growth, proliferation, invasion, and lymphangiogenesis assays.Results:RNF180 was silenced or down-regulated in 76.1%of GC tissues compared with 41.8% of paired non-tumor tissues. RNF180 protein expression in GC tissues was negatively related to the number of metastatic lymph nodes. RNF180 was down-regulated in 100% (7 of 7) of GC cell lines. Re-expression of RNF180 in HGC-27 GC cells reduced colony formation, proliferation, migration and invasion in vitro, and tumor growth and tumor lymphangiogenesis in mice it also down-regulated HGF, MMP-2, MMP-14, VEGF-C/D and CCR-7 in vitro, and Podoplanin in tumor tissue of mice.Conclusion:RNF180 is a suppressor gene involved inthe several biological events of GC cell including the proliferation, invasion, and tumor lymphangiogenesis.
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