Panoply™ Human MYC Over-expressing Stable Cell Line

ZNF706, encoded by a gene located on chromosome 8q22, is a C2H2 type zinc finger protein. Clinical studies have found that ZNF706 is upregulated in hepatocellular carcinoma (HCC), and high expression is associated with poor prognosis in HCC patients. Functional experiments showed that knockdown of ZNF706 inhibited the progression of HCC in vitro and in vivo. RNA sequencing (RNA-seq) and chromatin immunoprecipitation-based deep sequencing (ChIP-seq) revealed that ZNF706 is a key regulator of ferroptosis mechanistically, and SLC7A11 is an important target of ZNF706. Furthermore, ZNF706 knockdown inhibited SLC7A11 expression, increased lipid peroxidation, and promoted ferroptosis. Further analysis indicated that ZNF706 is a novel direct target for MYC transcriptional activation in HCC cells. Importantly, MYC loss reduced SLC7A11-mediated redox homeostasis, while re-expression of ZNF706 reversed this effect. In summary, these data indicate that ZNF706 is a potential oncogene in liver cancer and acts as a regulator of ferroptosis by regulating the expression of SLC7A11, thus constituting a potential therapeutic target for HCC.

To investigate the hypothetical mechanism by which MYC regulates ZNF706 expression, researchers constructed SNU-739 and LM3 hepatocellular carcinoma cells with stable MYC knockdown. In MYC knockdown cells, the mRNA and protein expression levels of ZNF706 and SLC7A11 were significantly reduced (Figure 1A and B). To further verify the effect of MYC on ZNF706 expression, researchers constructed MYC overexpressing SNU-739 and LM3 cells. Data showed that MYC overexpression significantly increased the expression levels of ZNF706 and SLC7A11 in HCC cells (Figure 1C and D). To investigate whether MYC binds to the ZNF706 promoter, they used the JASPAR database for prediction, revealing three potential MYC binding sites in the ZNF706 promoter region. Further analysis using a dual-luciferase reporter gene assay to detect the activation of the truncated ZNF706 promoter region revealed that the first binding site is the true MYC-recognized response element (Figure 1E). To further confirm the binding of MYC to the ZNF706 promoter, researchers performed ChIP-qPCR experiments, confirming a physical interaction between MYC and the ZNF706 promoter region (Figure 1F). In summary, these results indicate that MYC regulates ZNF706 expression in HCC cells through transcriptional activation.

Figure 1. MYC transcriptionally activates ZNF706. (Chu J, et al., 2024)