FIGURE 2.

GSTZ1 deficiency enhances glucuronic pathway activity. (A) Principal component analysis of metabolite signatures in Huh7 cells infected with AdGSTZ1 or AdGFP using a metabolomics assay. PC, primary component. (B) Heatmap of differentially expressed metabolites subjected to identical treatment conditions as in (A). (C) Overview of the glucuronic pathway. (D) Relative changes in intermediate metabolites of the glucuronic pathway. (E–G) Uridine 5′‐diphosphate glucuronic acid (UDP‐GlcUA) levels in GSTZ1‐OE Huh7 cells (E), GSTZ1‐KO SNU449 cells (F) and Gstz1 ^−/− mice liver tissues (G) quantified by the liquid chromatography‐tandem mass spectrometry (LC‐MS/MS)‐targeted metabolomics assay. (H) Transwell migration assays and quantification of the migrated cells in hepatoma cells supplemented with or without UDP‐GlcUA (0.5 mM for Huh7, 1 mM for SK‐Hep1, and 0.5 mM for SNU‐449) for 24 h. The migrated cells were stained with crystal violet staining. n = 3 independent experiments. (I) Representative immunofluorescence staining of E‐cadherin and vimentin from three independent experiments. Scale bar, 100 μm. Data are mean ± SD. p‐Values were derived from an unpaired, two‐tailed Student's t‐test in (D–F and H), and Mann–Whitney U test in (G) (**p < .01, ***p < .001).