Fig. 4: Glycolysis and lipid metabolic reprogramming in HPV-KI compared to HaCaT cells. | Cell Death & Disease

Fig. 4: Glycolysis and lipid metabolic reprogramming in HPV-KI compared to HaCaT cells.

From: Site-specific HPV18 integration facilitates cervical carcinogenesis through metabolic reprogramming-induced dysfunction of the SpHK1/S1P/S1PR1 pathway

Fig. 4

A GSEA Analysis based on the gene expression of Glycolysis/Gluconeogenesis Pathway in HPV-KI/HaCaT cells. B Gene expression and heatmap of Glycolysis/Glucogenesis associated genes were analyzed in HPV-KI and HaCaT. The green box in the heatmap indicates genes favoring PGAL consumption, while the pink box indicates genes involved in PGAL accumulation. C Hi-C contact heatmap at HK1 neighboring regions (chr10:71078602-71161637) was performed along with matching tracks of the ChIP-seq profile. The gene track is shown in the bottom panel. Red box indicates the H3K27ac peak of TSS and TES of HK1. D Heatmap analysis revealing the activity levels of HK, PFK and PK in HPV-KI/HaCaT cells. E Western blot depicting HK1/2 expression levels in HPV-KI/HaCaT cells, with GAPDH serving as control. F Metabolite abundance involved in Glycolysis/Glucogenesis between HPV-KI and HaCaT is visualized using a heatmap. G Boxplot illustrating the top fold changed metabolites associated with carbon metabolism in HPV-KI/HaCaT. Metabolites associated with glycolysis are highlighted in red bold. H KEGG analysis of metabolomic changes between HPV-KI and HaCaT base on DA score of carbon metabolism. I Diagram illustrating how Gro3P connects glycolysis to de novo GL synthesis, while SpHK1 is regulated by PA and links GL synthesis to sphingosine metabolism. J Assessment of GPDH activity in HPV-KI/HaCaT cells. K Quantification of LPA abundance, PA concentration, relative abundance of DAG in HPV-KI/HaCaT cells. Additionally, the S1P concentration in the culture medium supernatant is presented. L Assessment of SpHK1/2 activity in HaCaT and HPV-KI is shown. M Western blot showing SpHK1/2 expression levels in HPV-KI/HaCaT cells, with GAPDH serving as control. The data are calculated by two-tailed Student’s t-test. P value is denoted as *P < 0.05, **P < 0.01, and ***P < 0.001, ****P < 0.0001, “ns” represents “not significant”. N The overall survival of CESC cases from the TCGA cohort is stratified into high PGAL(+) and low PGAL(+) score groups using Kaplan-Meier analysis.

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