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. 2024 Feb 12;22:120. doi: 10.1186/s12964-023-01441-5

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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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