FAXDC2 inhibits the proliferation and invasion of human liver cancer HepG2 cells.
FAXDC2 inhibits the proliferation and invasion of human liver cancer HepG2 cells.
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DOI：
10.3892/etm.2023.12315
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发表时间：
2024-01
影响因子：
2.7
通讯作者：
Fan X
中科院分区：
文献类型：
--
作者：
Peng Z;Xu S;Zhang Q;Yang X;Yuan W;Wang Y;Li Y;Zhu P;Wu X;Jiang Z;Li F;Fan X
脂质代谢的重编程在肝癌的发生和发展中起重要作用。含脂肪酸羟化酶结构域2（FAXDC2）是一种参与胆固醇和鞘磷脂合成的羟化酶，在多种癌症中表达下调。目前尚无关于FAXDC2与肝癌发生之间关系的报道。本研究利用多个门户网站和公开可用的工具来探究其与肝癌的相关性。结果显示，FAXDC2在肝癌中的表达降低，其启动子附近的甲基化水平升高。肝癌患者中FAXDC2低表达者预后较差。通过功能获得和功能缺失策略来评估其在肝癌细胞中的作用。CCK - 8实验表明，FAXDC2的过表达抑制了肝癌细胞（HepG2）的活力。流式细胞术分析显示，FAXDC2过表达的HepG2细胞出现S期阻滞，同时细胞周期蛋白依赖性激酶2降低。Transwell实验表明，FAXDC2增加抑制了HepG2细胞的侵袭能力，同时伴有E - 钙黏蛋白的上调。值得注意的是，FAXDC2的敲低对细胞周期和侵袭功能无显著影响。基于cBioPortal平台，预测FAXDC2在肿瘤发生中与ERK信号密切相关。蛋白质印迹结果显示，FAXDC2的过表达降低了肝癌细胞中ERK的磷酸化水平。本研究首次确定FAXDC2为一种肝癌抑制因子，它可能通过与ERK信号相关的机制抑制肝癌细胞的增殖和侵袭。本研究为肝癌的诊断和治疗提供了一个可能的新靶点。
The reprogramming of lipid metabolism serves an important role in occurrence and development of liver cancer. Fatty acid hydroxylase domain containing 2 (FAXDC2) is a hydroxylase involved in the synthesis of cholesterol and sphingomyelin and downregulated in various types of cancer. There are no reports on the relationship between FAXDC2 and liver carcinogenesis. The present study used multiple portals and publicly available tools to explore its correlation with liver cancer. The results showed that the expression of FAXDC2 decreased in liver cancer and the methylation level near the promoter increased. Patients with liver cancer and with low expression of FAXDC2 had a poor prognosis. Gain of function and loss of function strategies were performed to evaluate its roles in liver cancer cells. CCK-8 assay showed that overexpression of FAXDC2 inhibited the viability of liver cancer cells (HepG2). Flow cytometry analysis indicated that HepG2 cells with overexpressing FAXDC2 showed an S phase arrest, associated with cyclin-dependent kinase 2 decreased. Transwell experiments showed that increasing FAXDC2 inhibited HepG2 cell invasion ability, accompanied by the upregulation of E-cadherin. Notably, knockdown of FAXDC2 had no significant effect on cell cycle and invasion functions. Based on the cBioPortal platform, FAXDC2 was predicted to closely correlate to the ERK signal in tumorigenesis. Western blotting results showed that overexpression of FAXDC2 decreased the phosphorylation level of ERK in liver cancer cells. The present study first identified FAXDC2 as a liver cancer suppressor, which might inhibit the proliferation and invasion of liver cancer cells through the mechanism associated with ERK signaling. The present study provided a possible new target for the diagnosis and treatment of liver cancer.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
2.4
作者：
Huynh H;Nguyen TT;Chow KH;Tan PH;Soo KC;Tran E
通讯作者：
Tran E
影响因子：
3.2
作者：
Takkunen, Minna;Grenman, Reidar;Virtanen, Ismo
通讯作者：
Virtanen, Ismo
DOI：
10.1016/j.apsb.2021.09.019
发表时间：
2022-03
期刊：
Acta pharmaceutica Sinica. B
影响因子：
--
作者：
Du D;Liu C;Qin M;Zhang X;Xi T;Yuan S;Hao H;Xiong J
通讯作者：
Xiong J
DOI：
10.1186/s40880-018-0301-4
发表时间：
2018-05-21
期刊：
Cancer communications (London, England)
影响因子：
--
作者：
Cheng C;Geng F;Cheng X;Guo D
通讯作者：
Guo D