Zhou Jun, Nie Wanpin, Yuan Jiajia, Zhang Zeyu, Mi Liangliang, Wang Changfa, Huang Ranglang
Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
Department of Hepatobiliary and Pancreatic Surgery, The Third Xiangya Hospital of The Central South University, Changsha, Hunan 410013, P.R. China.
Oncol Rep. 2021 Jun;45(6). doi: 10.3892/or.2021.8042. Epub 2021 Apr 13.
Cholangiocarcinoma (CCA) is the second most common type of hepatocellular carcinoma characterized by high aggressiveness and extremely poor patient prognosis. The germ cell‑specific gene 2 protein (GSG2) is a histone H3 threonine‑3 kinase required for normal mitosis. Nevertheless, the role and mechanism of GSG2 in the progression and development of CCA remain elusive. In the present study, the association between GSG2 and CCA was elucidated. Firstly, we demonstrated that GSG2 was overexpressed in CCA specimens and HCCC‑9810 and QBC939 cells by immunohistochemical (IHC) staining. It was further revealed that high expression of GSG2 in CCA had significant clinical significance in predicting disease deterioration. Subsequently, cell proliferation, apoptosis, cell cycle distribution and migration were measured by MTT, flow cytometry, and wound healing assays, respectively . The results demonstrated that downregulation of GSG2 decreased proliferation, promoted apoptosis, arrested the cell cycle and weakened migration in the G2 phase of CCA cells. Additionally, GSG2 knockdown inhibited CCA cell migration by suppressing epithelial‑mesenchymal transition (EMT)‑related proteins, such as N‑cadherin and vimentin. Mechanistically, GSG2 exerted effects on CCA cells by modulating the PI3K/Akt, CCND1/CDK6 and MAPK9 signaling pathways. experiments further demonstrated that GSG2 knockdown suppressed tumor growth. In summary, GSG2 was involved in the progression of CCA, suggesting that GSG2 may be a potential therapeutic target for CCA patients.
胆管癌（CCA）是第二常见的肝癌类型，具有高侵袭性且患者预后极差。生殖细胞特异性基因2蛋白（GSG2）是正常有丝分裂所需的组蛋白H3苏氨酸-3激酶。然而，GSG2在CCA进展和发展中的作用及机制仍不清楚。在本研究中，阐明了GSG2与CCA之间的关联。首先，我们通过免疫组织化学（IHC）染色证明GSG2在CCA标本以及HCCC-9810和QBC939细胞中过表达。进一步发现，CCA中GSG2的高表达在预测疾病恶化方面具有显著的临床意义。随后，分别通过MTT、流式细胞术和伤口愈合试验检测细胞增殖、凋亡、细胞周期分布和迁移。结果表明，GSG2的下调降低了CCA细胞的增殖，促进了凋亡，使细胞周期停滞，并削弱了G2期的迁移能力。此外，GSG2敲低通过抑制上皮-间质转化（EMT）相关蛋白（如N-钙黏蛋白和波形蛋白）来抑制CCA细胞迁移。机制上，GSG2通过调节PI3K/Akt、CCND1/CDK6和MAPK9信号通路对CCA细胞发挥作用。实验进一步证明，GSG2敲低抑制了肿瘤生长。总之，GSG2参与了CCA的进展，提示GSG2可能是CCA患者的潜在治疗靶点。
