The CASZ1 Knockout Huh-7 Polyclonal Cells product provides a ready-to-use CRISPR/Cas9-edited polyclonal population of Huh-7 human hepatocellular carcinoma cells with targeted disruption of the CASZ1 gene. This loss-of-function model enables direct investigation of CASZ1’s tumor suppressor functions in liver cancer biology, offering a genetically defined tool for elucidating molecular mechanisms driving hepatocellular carcinogenesis.
The Huh-7 parental cell line was established from a well-differentiated hepatocellular carcinoma of a 57-year-old Japanese male. Widely utilized in hepatocarcinoma research, Huh-7 cells support robust hepatitis C virus replication and retain hepatic drug-metabolizing enzyme activities, making them a clinically relevant platform for studying liver cancer biology, viral oncology, and pharmacological responses.
CASZ1 encodes a zinc finger transcription factor that acts as a critical tumor suppressor. Mechanistically, CASZ1 represses transcription of the oncogene MYCN and components of the Wnt/??-catenin pathway, while promoting p53-mediated apoptosis via upregulation of CDKN1A (p21) and BAX. It forms repressor complexes with REST, MTA2, and HDAC1, and its activity is modulated by upstream signals including TGF-??, BMP2, and p53. Additional downstream targets include MMP2 and VIM, linking CASZ1 to matrix remodeling and epithelial?Cmesenchymal transition.
In Huh-7 cells, disruption of CASZ1 abrogates its transcriptional silencing of MYCN and Wnt/??-catenin signaling, thereby enhancing proliferative drive and tumorigenicity. Simultaneously, impaired p53-dependent apoptosis and loss of TGF-??/SMAD-mediated growth suppression may contribute to increased migration and altered sensitivity to clinically used kinase inhibitors such as sorafenib. These phenotypic changes recapitulate key features of aggressive hepatocellular carcinoma, validating the model??s pathophysiological relevance.
This polyclonal knockout cell population is applicable in a range of experimental workflows. Proliferation can be quantified via MTT assays, migration by wound healing, and apoptosis signaling through western blot detection of cleaved caspase-3, p21, and MYCN. Transcriptomic consequences of CASZ1 loss can be captured by RNA-seq or RT-qPCR for EMT markers, while chromatin immunoprecipitation (ChIP?qPCR) identifies CASZ1-occupied genomic loci. Co-immunoprecipitation assays permit mapping of CASZ1 interactions with partners such as REST and HDAC1. The model also supports drug sensitivity profiling, including sorafenib response assessments. For further information and technical support, please contact Ascent Research.
