| OBJECTIVE: The aim of this study is to investigate the association of UBE2 C gene expression with the carcinogenesis and tumor progression of gastric adenocarcinoma and its relation with phosphorylation level of AURKA,and furthermore explore the possible mechanism as well.METHODS: Using eGWAS analysis found AURKA as a core regulator that connects several oncogenic signaling networks and found UBE2 C is closely related to AURKA.The expression levels of UBE2 C in gastric cancer cells transfected with si RNA against UBE2 C and a negative control were examined using real-time quantitative PCR and Western-blot analysis.Cell proliferation and Matrigel invasion assays were performed in gastric cancer cells transfected with si RNA.Furthermore,the expression of proteins downstream of the target gene UBE2 C were detected by Western-blot.The correlation between UBE2 C expression and AURKA in gastric cancer were analyzed by immunofluorescence and immunohistochemistry assays.RESULTS: Knockdown of UBE2 C inhibits the migration and proliferation of gastric cancer cells,and induces the cell apoptosis.In MGC-803 and SGC-7901 cells which UBE2C-deficient,G2/M phase arrest in the cell cycle and subsequently decreases gastric cancer tumorigenesis.Furthermore,knockdown of UBE2 C using si-RNA dramatically reduced the level of phosphorylation AURKA via Wnt/?-catenin and PI3K/Akt signaling pathways suppressed the occurrence and development of gastric cancer.Additionally,the expression of E-Cadherin was up-regulated and N-Cadherin was down-regulated in response to UBE2 C knockdown and inhibits EMT.CONCLUTION: In this study,we found the activity of AURKA might be regulated by UBE2 C.Knockdown of UBE2 C inhibited p-AURKA via Wnt/?-catenin and PI3K/Akt signaling pathways suppressed the occurrence and development of gastric cancer.Taken together,our data suggest UBE2 C may be a new marker in the diagnosis and a potential therapeutic target for the treatment of gastric cancer. |
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