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Proteintech iκbα
Wtap deletion in hepatocytes promotes hepatocellular carcinoma (HCC) progression in young mice. At 2 weeks old, male Wtap -HKO mice and Wtap flox/flox mice received a single intraperitoneal dose of DEN (50 mg/kg). Mice were fed either a normal choe (NC) diet or a high-fat diet (HFD) for 11 weeks. A , representative pictures of mouse livers from the indicated genotype are shown. B , tumor number was counted (n = 10–12 per group; NC: p = 0.0026; HFD: p < 0.0001). C , maximal tumor size was measured (n = 10–12 per group; NC: p < 0.0001; HFD: p < 0.0001). D , representative Ki67 staining photographs were shown. E , the number of Ki67-positive cells was counted (n = 6 per group; NC: p = 0.0002; HFD: p < 0.0001). F and G , triglyceride (TAG) levels in the livers of Wtap -HKO mice and Wtap flox/flox mice fed an NC diet for 35 weeks or an HFD for 11 weeks were assessed (n = 10 per group; F : p < 0.0001; G : p = 0.0012). H , serum-free fatty acid levels in Wtap -HKO mice and Wtap flox/flox mice fed with an NC diet for 11 weeks (n = 6–8 per group; p = 0.0022). I and J , immunoblotting of IGFBP1, CD36, CCL2, WTAP, <t>and</t> <t>Tubulin</t> in the livers of Wtap -HKO and Wtap flox/flox mice fed NC or HFD for 11 weeks following DEN treatment (n = 7 per group; n = 4 for representative images; NC: IGFBP1, p = 0.0033; CD36, p = 0.0013; and CCL2, p = 0.019; HFD: IGFBP1, p = 0.0115; CD36, p = 0.0264; and CCL2, p = 0.0011). K , heatmap of interleukin 6 (IL6) cytokine family ( Clcf1 , Cntf , Ctf1 , Il6 , IL11 , Il27 , Lif , and Osm ) and Tnfa in Wtap -HKO and Wtap flox/flox livers (n = 3 for each group, RNA-Seq data GSE168850). L , immunoblotting analysis of p-STAT3, STAT3, p-p65, p65, <t>p-IκBα,</t> IκBα, WTAP, and Tubulin in the livers of NC-fed Wtap -HKO and Wtap flox/flox mice pretreated with or without DEN (n = 7 for each group; n = 3 for representative images). ∗ p < 0.05; ∗∗ p < 0.01. Data represent the mean ± SD. CCL2, chemokine (C–C motif) ligand 2; DEN, diethylnitrosamine; IGFBP1, insulin-like growth factor–binding protein 1; Wtap -HKO, hepatocyte-specific Wtap knockout.
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1) Product Images from "Hepatocyte-specific Wtap deficiency promotes hepatocellular carcinoma by activating GRB2–ERK depending on downregulation of proteasome-related genes"

Article Title: Hepatocyte-specific Wtap deficiency promotes hepatocellular carcinoma by activating GRB2–ERK depending on downregulation of proteasome-related genes

Journal: The Journal of Biological Chemistry

doi: 10.1016/j.jbc.2023.105301

Wtap deletion in hepatocytes promotes hepatocellular carcinoma (HCC) progression in young mice. At 2 weeks old, male Wtap -HKO mice and Wtap flox/flox mice received a single intraperitoneal dose of DEN (50 mg/kg). Mice were fed either a normal choe (NC) diet or a high-fat diet (HFD) for 11 weeks. A , representative pictures of mouse livers from the indicated genotype are shown. B , tumor number was counted (n = 10–12 per group; NC: p = 0.0026; HFD: p < 0.0001). C , maximal tumor size was measured (n = 10–12 per group; NC: p < 0.0001; HFD: p < 0.0001). D , representative Ki67 staining photographs were shown. E , the number of Ki67-positive cells was counted (n = 6 per group; NC: p = 0.0002; HFD: p < 0.0001). F and G , triglyceride (TAG) levels in the livers of Wtap -HKO mice and Wtap flox/flox mice fed an NC diet for 35 weeks or an HFD for 11 weeks were assessed (n = 10 per group; F : p < 0.0001; G : p = 0.0012). H , serum-free fatty acid levels in Wtap -HKO mice and Wtap flox/flox mice fed with an NC diet for 11 weeks (n = 6–8 per group; p = 0.0022). I and J , immunoblotting of IGFBP1, CD36, CCL2, WTAP, and Tubulin in the livers of Wtap -HKO and Wtap flox/flox mice fed NC or HFD for 11 weeks following DEN treatment (n = 7 per group; n = 4 for representative images; NC: IGFBP1, p = 0.0033; CD36, p = 0.0013; and CCL2, p = 0.019; HFD: IGFBP1, p = 0.0115; CD36, p = 0.0264; and CCL2, p = 0.0011). K , heatmap of interleukin 6 (IL6) cytokine family ( Clcf1 , Cntf , Ctf1 , Il6 , IL11 , Il27 , Lif , and Osm ) and Tnfa in Wtap -HKO and Wtap flox/flox livers (n = 3 for each group, RNA-Seq data GSE168850). L , immunoblotting analysis of p-STAT3, STAT3, p-p65, p65, p-IκBα, IκBα, WTAP, and Tubulin in the livers of NC-fed Wtap -HKO and Wtap flox/flox mice pretreated with or without DEN (n = 7 for each group; n = 3 for representative images). ∗ p < 0.05; ∗∗ p < 0.01. Data represent the mean ± SD. CCL2, chemokine (C–C motif) ligand 2; DEN, diethylnitrosamine; IGFBP1, insulin-like growth factor–binding protein 1; Wtap -HKO, hepatocyte-specific Wtap knockout.
Figure Legend Snippet: Wtap deletion in hepatocytes promotes hepatocellular carcinoma (HCC) progression in young mice. At 2 weeks old, male Wtap -HKO mice and Wtap flox/flox mice received a single intraperitoneal dose of DEN (50 mg/kg). Mice were fed either a normal choe (NC) diet or a high-fat diet (HFD) for 11 weeks. A , representative pictures of mouse livers from the indicated genotype are shown. B , tumor number was counted (n = 10–12 per group; NC: p = 0.0026; HFD: p < 0.0001). C , maximal tumor size was measured (n = 10–12 per group; NC: p < 0.0001; HFD: p < 0.0001). D , representative Ki67 staining photographs were shown. E , the number of Ki67-positive cells was counted (n = 6 per group; NC: p = 0.0002; HFD: p < 0.0001). F and G , triglyceride (TAG) levels in the livers of Wtap -HKO mice and Wtap flox/flox mice fed an NC diet for 35 weeks or an HFD for 11 weeks were assessed (n = 10 per group; F : p < 0.0001; G : p = 0.0012). H , serum-free fatty acid levels in Wtap -HKO mice and Wtap flox/flox mice fed with an NC diet for 11 weeks (n = 6–8 per group; p = 0.0022). I and J , immunoblotting of IGFBP1, CD36, CCL2, WTAP, and Tubulin in the livers of Wtap -HKO and Wtap flox/flox mice fed NC or HFD for 11 weeks following DEN treatment (n = 7 per group; n = 4 for representative images; NC: IGFBP1, p = 0.0033; CD36, p = 0.0013; and CCL2, p = 0.019; HFD: IGFBP1, p = 0.0115; CD36, p = 0.0264; and CCL2, p = 0.0011). K , heatmap of interleukin 6 (IL6) cytokine family ( Clcf1 , Cntf , Ctf1 , Il6 , IL11 , Il27 , Lif , and Osm ) and Tnfa in Wtap -HKO and Wtap flox/flox livers (n = 3 for each group, RNA-Seq data GSE168850). L , immunoblotting analysis of p-STAT3, STAT3, p-p65, p65, p-IκBα, IκBα, WTAP, and Tubulin in the livers of NC-fed Wtap -HKO and Wtap flox/flox mice pretreated with or without DEN (n = 7 for each group; n = 3 for representative images). ∗ p < 0.05; ∗∗ p < 0.01. Data represent the mean ± SD. CCL2, chemokine (C–C motif) ligand 2; DEN, diethylnitrosamine; IGFBP1, insulin-like growth factor–binding protein 1; Wtap -HKO, hepatocyte-specific Wtap knockout.

Techniques Used: Staining, Western Blot, RNA Sequencing, Binding Assay, Knock-Out

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