GGCT participates in the malignant process of hepatocellular cancer cells by regulating the PTEN/PI3K/AKT pathway through binding to EZH2.

Abstract

Background: γ-Glutamylcyclotransferase (GGCT) is implicated in multiple types of cancer diseases. Nevertheless, the roles and relevant mechanisms of GGCT in hepatocellular carcinoma (HCC) remain vague.

Methods: GGCT expression in HCC and its effect on patient survival curve in HCC were evaluated utilizing the UALCAN database, along with western blot. CCK-8, EdU, and wound healing, together with transwell and western blot assays were adopted to assess the capabilities of cells to proliferate, migrate, invade, and epithelial-mesenchymal transition (EMT). Cell apoptosis was appraised utilizing TUNEL as well as western blot. Glycolysis was measured by western blot and kits. Enhancer of zeste homolog 2 (EZH2) expression in HCC cells was detected by western blot. Co-IP verified the combination of GGCT and EZH2. Moreover, PI3K/AKT pathway-related proteins were assessed employing western blot.

Results: GGCT expression was conspicuously upregulated in HCC samples and HCC cells. GGCT silencing repressed HuH-7 cell proliferative, invasive, and migratory capabilities as well as EMT, whereas facilitated cell apoptosis. In addition, GGCT silencing inhibited PTEN/PI3K/AKT pathway-mediated glycolysis. EZH2 was highly expressed in HCC cells and the interaction of GGCT and EZH2 was verified. Overexpression of EZH2 reversed the effects of GGCT silencing on HuH-7 cell proliferation, migration, invasion, cell apoptosis, and glycolysis. Moreover, the PTEN inhibitor SF1670 reversed the effects of GGCT silencing and EZH2 overexpression on the glycolysis and malignant process in HuH-7 cells.

Conclusion: In conclusion, GGCT silencing restrained the proliferation and metastasis, and promoted apoptotic levels of HCC cells via regulating PTEN/PI3K/AKT pathway-mediated glycolysis, which might offer a prospective candidate in treating HCC.