Fig. 1.

CDK7 is a potential therapeutic target for liver cancer. a Schematic outline of the stress lethality screen. Pooled kinome CRISPR screens were performed in Hep3B and Huh7 cells. b A set of CDKs was identified as stress lethal hits in both Hep3B and Huh7 cells. c Gene expression levels of CDK7 in the cohort of GSE14520 (n = 213) and TCGA database (n = 50). d Association of CDK7 expression with prognosis in HCC patients (n = 80). e The level of CDK7 knockdown in HCC cell lines was measured by western blot. f, g Viability was assessed by IncuCyte assay and colony formation assay. h Liver cancer cell lines were treated with increasing concentrations of THZ1 for about 2 weeks. Viability was assessed by colony formation assay. i Representative images of control and THZ1-treated cells in the presence of a caspase-3/7 activatable dye. j Immunoblotting analysis of MYC level in a panel of HCC cell lines. k Short-term growth inhibition assay of THZ1 in the panel of HCC cell lines. l Knockdown of MYC impairs cell proliferation in MYC high-expressed cells. m THZ1 can selectively suppress tumor growth in MYC high-expressed xenograft models (10 mg/kg intraperitoneal, twice daily). Mean tumor volumes ± SEM are shown (n = 5–7 mice per group). *P < .05, ***P < .001