GSTZ1-1 downregulates Wnt/β-catenin signalling in hepatocellular carcinoma cells.

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.