Fig. 4

USP22 sustains the mitochondrial biogenesis program, associated with a poor survival outcome in BLBC and HER2⁺-BC patients: A Radar plot with all strongly enriched gene sets from the curated collection of "hallmark of cancer" gene sets indicates the "HALLMARK_OXIDATIVE_PHOSPHORYLATION" (OXPHOS) as the only commonly enriched gene set upon USP22 loss in all studied (non-)cancer models as well as in TNBC cells (accession number of all datasets is provided in Methods and Supplementary data). B Volcano plot of differentially expressed genes upon USP22 silencing in HCC1806 cells (TNBC) after 72 h of transfection (cut-off: |log2 fold change|≥ 0.7; p-val < 0.05 and basemean ≥ 15). C GSEA profiles of the "HALLMARK_OXIDATIVE_PHOSPHORYLATION" gene set enriched in all studied datasets with USP22 interference. NES: Normalized Enrichment Score. D GSEA of mitochondria-related gene sets in all studied USP22-deficient entities (gene set source: www.broadinstitute.org/mitocarta/mitocarta30-inventory-mammalian-mitochondrial-proteins-and-pathways). Values on the top of the bars represent the NES for each significantly enriched gene set. E Dot plot (upper left panel) of enriched gene sets from the curated collection of "REACTOME" gene sets in USP22^high BLBC and HER2⁺-BC patients (TCGA-BRCA) demonstrates two OXPHOS-related gene sets as significantly enriched in both cancer entities. The GSEA profile the "REACTOME_MITOCHONDRIAL_BIOGENESIS" is also shown in both cancer entities (upper right panel). Patient survival analysis robustly associates BLBC and HER2⁺-BC patients characterized by heightened expression of the "REACTOME_MITOCHONDRIAL_BIOGENESIS" gene set with a poor survival outcome (low panel). NES: Normalized enrichment score, source of patient transcriptomic and follow-up data: https://portal.gdc.cancer.gov/. F Uniform Manifold Approximation and Projection (UMAP) plots of USP22, TFAM, SURF1 and SDHA expression in TNBC, HER2⁺ and ER⁺ BC biopsies at a single cell level. Correlation analysis of USP22 with the same OXPHOS gene panel in TNBC and HER2⁺-BC biopsies at a single cell level (lower panel). Data were retrieved from https://singlecell.broadinstitute.org/single_cell