Abstract

BackgroundGamma glutamylcyclotransferase (GGCT) has been proved to be involved in various cancers, but the biological function of GGCT in gastric cancer is still largely unknown. MethodsThe expression level of GGCT was evaluated by informatics analyses based on the Oncomine database. GGCT gene was then effectively knocked down via lentivirus mediated short hairpin RNA (shRNA) system. Then a series of functional assays, including MTT, colony formation and flow cytometry analysis were conducted on gastric cancer cells following GGCT knockdown.ResultsWe found GGCT is commonly up-regulated in gastric cancer tissues. Furthermore, MTT analysis showed that GGCT depletion significantly inhibited cell proliferation in MGC80-3 and AGS cells. Colony formation assay revealed that depletion of GGCT reduced the colony formation ability in gastric cancer cells. What’s more, cell cycle analysis showed that depletion of GGCT induced gastric cancer cell cycle arrested G2/M phase. More importantly, cell apoptosis analysis further revealed that GGCT inhibition induced early and late cell apoptosis in gastric cancer.ConclusionThis study suggests GGCT is essential for gastric cancer proliferation and its downregulation may provide a potential anticancer therapy for gastric cancer.

Highlights

  • Gamma glutamylcyclotransferase (GGCT) has been proved to be involved in various cancers, but the biological function of GGCT in gastric cancer is still largely unknown

  • GGCT mRNA was overexpressed in gastric cancer As GGCT has been reported to be upregulated in several cancers, we conducted a review of previous microarray data for the expression of GGCT on mRNA level in human gastric cancers

  • Lenti-shGGCT reduces GGCT expression in human gastric cancer MGC80-3 and AGS cells To explore the role GGCT plays in human gastric cancer, a lentiviral vector system expressing short hairpin RNA (shRNA) against GGCT was constructed in MGC80-3 and AGS cells

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Summary

Introduction

Gamma glutamylcyclotransferase (GGCT) has been proved to be involved in various cancers, but the biological function of GGCT in gastric cancer is still largely unknown. As a common cancer, has the third highest mortality rate in both sexes worldwide, especially in developing countries and regions [1]. Lack of effective early diagnostic methods makes gastric cancer usually be diagnosed at late stages and missed the best treatment time for curative surgery and radiotherapy [2, 3]. Early diagnosis and targeted therapy are critical for better prognosis of gastric cancer in the future. It has been reported that multiple gene abnormalities led to the initiation and development of gastric cancer [4]. Investigating the underling mechanisms and identifying key genes of gastric

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