Expression of dUTPase in Gastric Cancer and Its Effect on Proliferation and Migration of Cancer Cells
JIANG Zhen1,2, XIE Jiebin3, XIAO Yang1,2, LUO Yaomin1,2, WEI Chen1,2, YUAN Xiaoxia1,2,4*
dUTPase (deoxyuridine 5’-triphosphate nucleotidohydrolase) encoded by DUT gene is a key enzyme in the DNA synthesis process. Recent studies have shown that it acts as a “House keeper” in the protection of genome stability, but its expression and roles in gastric cancer are still unclear. In this study, iTRAQ-labeled quantitative proteomics was used to identify the high expression of dUTPase in gastric cancer tissue samples. TIMER database analysis confirmed that dUTPase was highly expressed in gastric cancer. The results of qPCR (quantitative real-time PCR) and IHC (immunohistochemistry) showed that the expression of dUTPase was significantly higher in gastric cancer tissues, its expression was correlated with clinicopathological factors such as histological grade and TNM stages. Prognostic analysis showed that high expression of dUTPase was associated with FP (first progression survival), OS (overall survival), PPS (post progression survival) and HER2 positive status. GSEA (gene set enrichment analysis) showed that 185 signaling pathways were significantly activated in gastric cancer patients with high expression of DUT, involving DNA synthesis, DNA repair and genome stability. A series of in vitro functional experiments showed that inhibition of DUT gene expression in vitro could significantly inhibit the proliferation and the migration of gastric cancer cells. In conclusion, this study confirmed that dUTPase was significantly overexpressed in gastric cancer, and its expression might activate multiple tumor signaling pathways involved in DNA synthesis, DNA repair, and genomic stability. Targeting dUTPase can significantly inhibit the proliferation and migration of gastric cancer cells.
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