RESUMEN
RAB18, a member of the Ras family, has been suggested to play a critical role in multiple biological process. However, its functions in the development of hepatocellular carcinoma (HCC) remain unknown. In the present study, the expression and biological role of RAB18 in HCC were investigated. Results showed that the expression level of RAB18 was significantly increased in HCC tissue specimens and HCC cell lines. Kaplan-Meier survival analysis showed that high RAB18 expression was correlated with poor overall survival compared to those with low RAB18 expression. These results were further confirmed by analyses in the Cancer Genome Atlas (TCGA) database. Specific knockdown of RAB18 expression inhibited proliferation and clone formation of HCC in vitro. Western blot analyses showed that CCND1 was suppressed, and p21 and p27 were substantially upregulated in RAB18 knockdown HCC cells. Furthermore, we also observed that knockdown of RAB18 expression suppressed the migration and invasion of HCC cells and reversed expression of epithelial-mesenchymal transition (EMT)-related markers. Interestingly, the primary and xenograft tumor mouse models showed that RAB18 knockdown significantly reduced in vivo tumorigenesis and metastasis in nude mice. These results revealed that RAB18 was correlated with poor clinical outcomes and facilitated HCC progression via promotion of HCC cell proliferation and metastasis. These findings suggest that RAB18 may be a prognostic biomarker and potential therapeutic target in patients with HCC.
RESUMEN
OBJECTIVE: To study the effect of tumor necrosis factor-alpha (TNF-alpha) on the morphology and ultrastructure of dendritic cells (DCs). METHODS: Freshly isolated precursors of DCs were cultured in the medium consisting of RPMI 1640 medium and 10 % inactivated fetal bovine serum. In one experiment, the cells were pretreated by TNF-alpha (200 U/ml) for 4 h, followed by treatment with human granulocyte macrophage colony stimulating factor (rhGM-CSF, 800 U/ml) and interleukin-4 (IL-4, 500 U/ml). The above treatments were repeated again every 48 h. The cells in another experiment were treated with rhGM-CSF (800 U/ml) and IL-4 (500 U/ml) on the day of in vitro culture, which was repeated every 48 h with a treatment with TNF-alpha (200 U/ml) on day 5 of cell culture. On day 8, the cells in the 2 parallel experiments were collected with the former cells designated as T-DC and the latter DC. Morphological differences between the 2 group of cells were observed using light microscope and scanning electron microscope. RESULTS: The T-DC exhibited more typical dendric processes than DCs did. CONCLUSION: Pretreatment of the precursors of DCs with TNF-alpha for 4 h, in comparison with TNF-alpha treatment on day 5 of cell culture, produced DCs with more typical and conspicuous dendric morphologies.
