GPX8受FOXC1转录调控，并通过激活Wnt信号通路促进胃癌细胞的生长。
GPX8 is transcriptionally regulated by FOXC1 and promotes the growth of gastric cancer cells through activating the Wnt signaling pathway.
作者信息
Chen Hong, Xu Lu, Shan Zhi-Li, Chen Shu, Hu Hao
机构信息
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Soochow University, No.899, Pinghai Road, Suzhou, 215000, Jiangsu, China.
Department of General Surgery, Suzhou Dushu Lake Hospital Affiliated to Soochow University, Suzhou, 215000, Jiangsu, China.
出版信息
Cancer Cell Int. 2020 Dec 14;20(1):596. doi: 10.1186/s12935-020-01692-z.
BACKGROUND
Glutathione Peroxidase 8 (GPX8) as a member of the glutathione peroxidase (GPx) family plays an important role in anti-oxidation. Besides, dysregulation of GPX8 has been found in gastric cancer, but its detailed molecular mechanism in gastric cancer has not been reported.
METHODS
Our study detected the expression of GPX8 in gastric cancer tissues and cell lines using immunohistochemistry (IHC), western blot and qRT-PCR, and determined the effect of GPX8 on gastric cancer cells using CCK-8, colony formation, transwell migration and invasion assays. Besides, the effect of GPX8 on the Wnt signaling pathway was determined by western blot. Furthermore, the transcription factor of GPX8 was identified by bioinformatics methods, dual luciferase reporter and chromatin immunoprecipitation (CHIP) assays. In addition, the effect of GPX8 on tumor formation was measured by IHC and western blot.
RESULTS
The over-expression of GPX8 was observed in gastric cancer tissues and cells, which facilitated the proliferation, migration and invasion of gastric cancer cells as well as the tumor growth. GPX8 knockdown effectively inhibited the growth of gastric cancer cells and tumors. Moreover, GPX8 could activate the Wnt signaling pathway to promote the cellular proliferation, migration and invasion through. Furthermore, FOXC1 was identified as a transcription factor of GPX8 and mediated GPX8 expression to affect cell development processes.
CONCLUSIONS
These findings contribute to understanding the molecular mechanism of GPX8 in gastric cancer. Additionally, GPX8 can be a potential biomarker for gastric cancer therapy.
背景
谷胱甘肽过氧化物酶8（GPX8）作为谷胱甘肽过氧化物酶（GPx）家族的一员，在抗氧化过程中发挥重要作用。此外，已发现在胃癌中GPX8表达失调，但其在胃癌中的详细分子机制尚未见报道。
方法
本研究采用免疫组织化学（IHC）、蛋白质免疫印迹法和qRT-PCR检测GPX8在胃癌组织和细胞系中的表达，并使用CCK-8、集落形成、transwell迁移和侵袭实验来确定GPX8对胃癌细胞的影响。此外，通过蛋白质免疫印迹法确定GPX8对Wnt信号通路的影响。进一步地，通过生物信息学方法、双荧光素酶报告基因和染色质免疫沉淀（CHIP）实验鉴定GPX8的转录因子。另外，通过免疫组织化学和蛋白质免疫印迹法检测GPX8对肿瘤形成的影响。
结果
在胃癌组织和细胞中观察到GPX8过表达，其促进了胃癌细胞的增殖、迁移和侵袭以及肿瘤生长。敲低GPX8可有效抑制胃癌细胞和肿瘤的生长。此外，GPX8可激活Wnt信号通路，通过该通路促进细胞增殖、迁移和侵袭。此外，FOXC1被鉴定为GPX8的转录因子，并介导GPX8表达以影响细胞发育过程。
结论
这些发现有助于理解GPX8在胃癌中的分子机制。此外，GPX8可能成为胃癌治疗的潜在生物标志物。
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