GSTZ1-1 downregulates Wnt/β-catenin signalling in hepatocellular carcinoma cells
GSTZ1-1 downregulates Wnt/β-catenin signalling in hepatocellular carcinoma cells
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GSTZ1-1 下调肝细胞癌细胞中的 Wnt/β-catenin 信号传导
DOI：
10.1002/2211-5463.12769
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发表时间：
2019-12-10
期刊：
影响因子：
2.6
通讯作者：
Wang, Kai
中科院分区：
文献类型：
--
作者：
Lei, Chong;Wang, Qiujie;Wang, Kai
谷胱甘肽S-转移酶Zeta 1-1（GSTZ 1 -1）是一种参与苯丙氨酸催化和异生物质解毒的酶，在肝细胞癌（HCC）中起肿瘤抑制作用，但其潜在机制仍不清楚。本研究通过RNA测序对GSTZ 1 -1基因进行转录组分析，进一步探讨其在肝癌中的功能。分析显示，在GSTZ 1 -1过表达的Huh 7细胞中，223个基因上调，290个基因下调。基因本体分析表明，这些差异表达基因（DEG）高度富集蛋白磷酸化，细胞周期停滞和代谢过程。通路分析显示，代谢途径是上调基因中主要的富集通路，而TGF-β和Wnt/β-连环蛋白信号通路在下调的簇中突出。通路相互作用网络也表明Wnt/β-catenin通路位于簇的中心。通过qRT-PCR验证所选DEG的表达水平，并通过体外和体内荧光素酶测定、蛋白质印迹和免疫组织化学分析验证Wnt/β-连环蛋白参与。这些结果提供了GSTZ 1 -1过表达Huh 7细胞中转录组的全面概述，并表明GSTZ 1 -1可能通过灭活Wnt/β-连环蛋白信号通路发挥肿瘤抑制作用。
Glutathione S-transferase Zeta 1-1 (GSTZ1-1), an enzyme involved in the catabolism of phenylalanine and the detoxification of xenobiotics, plays a tumour suppressor role in hepatocellular carcinoma (HCC), but the underlying mechanism remains largely unknown. Here, we further explored the function of GSTZ1-1 in HCC through transcriptome analysis by RNA sequencing. The analysis revealed that 223 genes were upregulated and 290 genes were downregulated in GSTZ1-1-overexpressing Huh7 cells. Gene Ontology analysis showed that these differentially expressed genes (DEGs) were highly enriched for protein phosphorylation, cell cycle arrest and metabolic processes. Pathway analysis revealed that metabolic pathways were the predominant enriched pathways among the upregulated genes, while the TGF-beta and Wnt/beta-catenin signalling pathways were prominent in the downregulated clusters. Pathway interaction networks also showed that the Wnt/beta-catenin pathway was located in the centre of the cluster. The expression levels of selected DEGs were validated by qRT-PCR, and Wnt/beta-catenin involvement was validated by luciferase assays, western blotting and immunohistochemical analysis in vitro and in vivo. These results provide a comprehensive overview of the transcriptome in GSTZ1-1-overexpressing Huh7 cells and indicate that GSTZ1-1 may play a tumour suppressor role by inactivating the Wnt/beta-catenin signalling pathway.