Fig. 1: Depletion of GASC1 suppresses HCC proliferation and tumor growth.
From: GASC1 promotes hepatocellular carcinoma progression by inhibiting the degradation of ROCK2
a Distribution of alteration frequency in GASC1 gene in multiple cancer types. Details of the corresponding tumor data set and the year of publication were indicated in parentheses. CNA copy-number alteration. b Empirical cumulative distribution function (CDF) plots showing correlation of individual tumors with GASC1 signature across various tumor grades within the HCC cohort. c CDF plots showing correlation of individual tumors with GASC1 signature across various clinical stages within the HCC cohort. d CDF plots showing correlation of individual tumors with GASC1 signature across various tumor size within the HCC cohort. e Kaplan–Meier survival curves comparing subjects in the TCGA HCC cohort stratified by correlation with GASC1 signature. Tumor samples were binned according to their gene expression correlation with GASC1 signature. Subjects harboring the top 30% (n = 99) most correlated tumors exhibited significantly decreased survival as compared to the remaining subjects (n = 231) from the TCGA HCC cohort. f Efficiency of colony-formation was examined in GASC1 shRNA (shGASC1) and Non-targeting shRNA (NT) treated Hep3B and MHCC-97H cells 2–3 weeks after plating. Data are presented as mean ± SEM of three independent experiments. ***P < 0.001 by Student’s t test. g, h GASC1 depletion affects tumor growth in mouse xenograft. GASC1 depletion was achieved by inducible shRNA treatment (g) or genome editing by GASC1 CRISPR-Cas9 (h). Mice were sacrificed 34 days (Hep3B) or 26 days (MHCC-97H) after implantation. Tumor image (left panel) and tumor weight (middle panel) are presented. Tumor growth was measured at the indicated time points and tumors were dissected at the endpoint (n = 10–12 tumors) (right panel). Data are presented as mean ± SEM. **P < 0.01 and ***P < 0.001 by two-way ANOVA. i Representative images of Ki-67 immunohistochemistry (IHC) staining in the sgCtrl and the sgGASC1 tumor groups (H). Scale bar: 20 μM. j Kaplan–Meier survival curve of mice with orthotopic liver tumor induced by intrahepatic implantation of Hep3B cells transfected with shGASC1 or NT shRNA. k Kaplan–Meier analysis of GASC1 expression and overall survival of HCC patients (N = 142).
