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GGCT通过与EZH2结合来调节PTEN/PI3K/AKT通路，从而参与肝癌细胞的恶性进程。

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

作者信息

He Junbo, Wang Liangzhi, Lv Mengjia, Yuan Yiming

机构信息

Department of General Practice, The Third Affiliated Hospital of Soochow University, No. 185, Jiuqian Street, Changzhou, 213003, Jiangsu, China.

出版信息

Discov Oncol. 2025 Feb 7;16(1):129. doi: 10.1007/s12672-025-01882-z.

DOI:10.1007/s12672-025-01882-z
PMID:39918720
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11806167/
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.

摘要

背景

γ-谷氨酰环转移酶（GGCT）与多种癌症疾病相关。然而，GGCT在肝细胞癌（HCC）中的作用及相关机制仍不明确。

方法

利用UALCAN数据库及蛋白质印迹法评估GGCT在HCC中的表达及其对HCC患者生存曲线的影响。采用CCK-8、EdU、伤口愈合实验以及Transwell实验和蛋白质印迹法评估细胞的增殖、迁移、侵袭及上皮-间质转化（EMT）能力。利用TUNEL法及蛋白质印迹法评估细胞凋亡。通过蛋白质印迹法和试剂盒检测糖酵解。采用蛋白质印迹法检测HCC细胞中zeste同源物2增强子（EZH2）的表达。免疫共沉淀验证GGCT与EZH2的结合。此外，采用蛋白质印迹法评估PI3K/AKT通路相关蛋白。

结果

GGCT在HCC样本和HCC细胞中的表达显著上调。GGCT沉默抑制了HuH-7细胞的增殖、侵袭和迁移能力以及EMT，同时促进了细胞凋亡。此外，GGCT沉默抑制了PTEN/PI3K/AKT通路介导的糖酵解。EZH2在HCC细胞中高表达，且验证了GGCT与EZH2的相互作用。EZH2过表达逆转了GGCT沉默对HuH-7细胞增殖、迁移、侵袭、细胞凋亡和糖酵解的影响。此外，PTEN抑制剂SF1670逆转了GGCT沉默和EZH2过表达对HuH-7细胞糖酵解和恶性进程的影响。

结论

总之，GGCT沉默通过调节PTEN/PI3K/AKT通路介导糖酵解抑制了HCC细胞的增殖和转移，并提高了细胞凋亡水平，这可能为HCC治疗提供一个有前景的候选方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d99/11806167/7c39102b1646/12672_2025_1882_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d99/11806167/5ecdb4d2dad3/12672_2025_1882_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d99/11806167/fee4954b66eb/12672_2025_1882_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d99/11806167/4b4959822722/12672_2025_1882_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d99/11806167/bfc3e88f4ea8/12672_2025_1882_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d99/11806167/010a5ffae5af/12672_2025_1882_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d99/11806167/7c39102b1646/12672_2025_1882_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d99/11806167/5ecdb4d2dad3/12672_2025_1882_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d99/11806167/fee4954b66eb/12672_2025_1882_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d99/11806167/4b4959822722/12672_2025_1882_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d99/11806167/bfc3e88f4ea8/12672_2025_1882_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d99/11806167/010a5ffae5af/12672_2025_1882_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d99/11806167/7c39102b1646/12672_2025_1882_Fig6_HTML.jpg

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