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. 2022 Nov 24;41:330. doi: 10.1186/s13046-022-02528-6

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© The Author(s) 2022

Open AccessThis 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. 3 — UBR7 inhibits glycolysis by negatively regulating HK2. A Left: heatmap summarising genes differentially expressed in the Alb-Cre;UBR7^fl/fl livers compared to UBR7^WT (WT) livers via RNA-sequencing (RNA-seq) analysis. Right: volcano plots of the differentially expressed genes with 104 up-regulated genes and 369 down-regulated genes. B Left: Gene Ontology (GO) analysis showed different genes in (A). Right: Gene Set Enrichment Analysis (GSEA) output images of two chosen pathways displaying a correlation of differentially regulated genes in Alb-Cre;UBR7^fl/fl liver with the “Metabolism core gene” set and “HK2-based core gene” set. C Immunohistochemical and Western blot analysis of the expression level of HK2 in Alb-Cre;UBR7^fl/fl and WT liver. D WT and Alb-Cre;UBR7^fl/fl mouse primary liver cells were analysed for glycolysis efficiency, the oxygen consumption rate (OCR), glucose uptake and lactate secretion levels. E, F Glycolysis efficiency, the oxygen consumption rate (OCR), glucose uptake and lactate secretion levels were detected in UBR7 overexpressing BEL-7402 or UBR7 knockout HepG2 cells. Data are shown as mean ± SD of three independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001. The scale bar in (C) is 100 μm