Fig. 1: Overexpression of spliceosome components associates with HCC pathogenesis and conditional USP39 overexpression enhances in vivo hepatocarcinogenesis.
A Proteomic subgroups were identified based on differentially expressed proteins between tumor and non-tumor tissues from the CPTAC HCC cohort. Each column represents a patient sample and rows indicate proteins. The color of each cell shows the Z-score (log2 of relative abundance scaled by protein SD) of the protein in that sample. B HR heatmap representing associations between spliceosomal gene expression and OS across 33 different cancer types profiled using TCGA. The HR for the high expression group versus the low expression group (median expression value as a cut-off) was calculated. The heatmap is colored based on the log10 HR. A square with a bold border represents a p-value < 0.05 in the survival analysis. Each column represents a cancer type, and rows indicate genes arranged in the order of spliceosome assembly (A: complex A, B: complex B, Bact: complex B catalytic active, C: complex C). C Schematic summary of the DEN/CCl4-induced hepatocarcinogenesis model established in Usp39HOE and control mice (WT). Images of tumor-bearing livers are shown. D Body weight, liver weight, liver/body weight ratios, and tumor numbers of WT and Usp39HOE mice were measured. ns: not significant. E USP39 and cell cycle-related proteins including CCND1, CDK2, and CDK6 were detected with WB. F Immunohistochemistry was performed to examine the expression of Ki67 and CCND1 in WT and Usp39HOE mice. The IHC-positive hepatocytes were then counted. Three high-power fields (HPF, ×800 magnification) were obtained from each mouse (n = 3). Scale bar, 100 μm. Mean ± SD. P values were determined using an unpaired Student’s t-test. ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001. (Experimental group, n = 5; control group, n = 8).
