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首页> 外文期刊>FEBS Open Bio >GSTZ1‐1 downregulates Wnt/β‐catenin signalling in hepatocellular carcinoma cells
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GSTZ1‐1 downregulates Wnt/β‐catenin signalling in hepatocellular carcinoma cells

机译：GSTZ1-1下调肝细胞癌细胞中的WNT /β-连环蛋白信号传导

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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‐β and Wnt/β‐catenin signalling pathways were prominent in the downregulated clusters. Pathway interaction networks also showed that the Wnt/β‐catenin pathway was located in the centre of the cluster. The expression levels of selected DEGs were validated by qRT‐PCR, and Wnt/β‐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/β‐catenin signalling pathway.
机译：谷胱甘肽S-转移酶Zeta 1-1（GSTZ1-1），涉及苯丙氨酸分解代谢的酶和异种症的解毒，在肝细胞癌（HCC）中起肿瘤抑制作用，但下面的机制仍然很大程度上是未知的。这里，我们进一步通过RNA测序探讨了通过转录组分析通过转录组分析的GSTZ1-1在HCC中的功能。该分析显示，上调223个基因，在GSTZ1-1过表达HUH7细胞中下调290个基因。基因本体学分析表明，这些差异表达的基因（DEGS）高度富集用于蛋白质磷酸化，细胞周期停滞和代谢过程。途径分析显示，代谢途径是上调基因中的主要富集的途径，而TGF-β和Wnt /β-catenin信号传导途径在下调的簇中突出。途径相互作用网络还显示WNT /β-连环蛋白途径位于簇的中心。通过QRT-PCR验证所选DEG的表达水平，并通过荧光素酶测定，β-蛋白酶测定，β-体外和免疫组化分析验证WNT /β-Catenin受累。这些结果在GSTZ1-1-过表达HUH7细胞中综合概述了转录组，并表明GSTZ1-1可以通过灭活WNT /β-Catenin信号传导途径来发挥肿瘤抑制作用。

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