The KHSRP Knockout SK-HEP-1 Polyclonal Cells represent a polyclonal population of SK-HEP-1 human liver adenocarcinoma cells with CRISPR/Cas9-mediated disruption of the KHSRP gene. This loss-of-function model is generated using CRISPR/Cas9 technology to disrupt the target gene, yielding a heterogeneous pool that captures diverse editing outcomes and ensures robust functional ablation. Unlike monoclonal lines, this format avoids clonal selection bias, making it suitable for studies requiring population-level responses.
The SK-HEP-1 cell line, derived from the ascitic fluid of a hepatocellular carcinoma patient, is a well-established model for liver adenocarcinoma. These epithelial cells display malignant properties such as anchorage-independent growth and tumorigenicity, and have been extensively used to study hepatocarcinogenesis, signaling pathways, epithelial-mesenchymal transition, and drug resistance.
KHSRP (KH-type splicing regulatory protein) is an RNA-binding protein that recognizes AU-rich elements (AREs) in target mRNAs, primarily promoting their decay via recruitment of the exosome complex. Key targets include CTNNB1, c-Myc, IL-8, and TNF-?? transcripts. By destabilizing CTNNB1 mRNA, KHSRP directly suppresses Wnt/??-catenin signaling output. Its activity is modulated by p38 MAPK-mediated phosphorylation in response to stress or TNF-??, and it interacts with hnRNP A1, UPF1, and the Drosha/DGCR8 complex to coordinate mRNA metabolism and microRNA processing. KHSRP belongs to a family of ARE-binding proteins that includes TTP and HuR, which collectively determine the fate of labile mRNAs. Thus, KHSRP integrates inflammatory and stress signals to control gene expression at the post-transcriptional level.
In the context of hepatocellular carcinoma, KHSRP disruption is particularly significant because Wnt/??-catenin and NF-??B pathways are frequently hyperactivated. Loss of KHSRP in SK-HEP-1 cells is predicted to stabilize CTNNB1 and c-Myc mRNAs, leading to increased ??-catenin protein and enhanced TCF/LEF-mediated transcription that drives proliferation and survival. Concurrently, impaired decay of inflammatory transcripts such as IL-8 and TNF-?? may potentiate autocrine and paracrine signaling loops that contribute to tumor progression and immune evasion. This polyclonal knockout model enables dissection of KHSRP’s tumor-suppressive functions in mRNA decay and its broader impact on liver cancer biology, without the confounding effects of clonal selection.
This product is ideally suited for functional studies including post-transcriptional gene regulation analysis, hepatocellular carcinoma biology, mRNA stability measurement, and drug resistance mechanism investigation. Typical downstream assays include western blotting and RT-qPCR to validate target expression changes, RNA immunoprecipitation to assess protein-RNA interactions, RNA-seq for transcriptome-wide profiling, luciferase reporter assays to monitor ARE-mediated regulation, and cell proliferation and migration assays to evaluate phenotypic outcomes. The polyclonal format is especially advantageous for pooled screening approaches and for experiments that prioritize population heterogeneity over clonal uniformity. For further details or technical support, please contact Ascent Research.
