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. 2024 Aug 12;5(8):e684. doi: 10.1002/mco2.684

FIGURE 4.

FIGURE 4

USP22 potentiates melanoma metastasis and EMT through activating PI3K/Akt/mTOR pathway. (A) Transcriptome sequencing was performed on USP22‐knockdown (shUSP22) and control (shCtrl) A375 cells and the results were visualized in a heatmap. (B) RNA sequencing based on KEGG pathways enrichment shows the top 10 enriched pathways in USP22‐knockdown A375 cells. (C) Gene Set Enrichment Analysis (GSEA) showing PI3K–Akt pathway and EMT signatures were enriched in control group (shCtrl) based on RNA sequencing. (D) GSEA showing PI3K–Akt pathway and EMT signatures were enriched in USP22‐high group based on Xiangya cohort. (E) The protein expression levels of Akt, p‐Akt (Ser473), mTOR, p‐mTOR (Ser2448) in USP22‐knockout (sgUSP22) and USP22‐overexpressing (USP22) A375 cells quantified by western blotting. (F and G) Transwell assay showing effect of GDC0941 (PI3Ki, 1 µM), MK2206 (Akti, 8 µM), AZD8055 (mTORi, 500 nM) on the role of USP22 silencing (sgUSP22) in A375 cell migration. Two‐way ANOVA analysis was performed in (G). Ns., not significance; ****p < 0.0001.