A novel MYC-ZNF706-SLC7A11 regulatory circuitry contributes to cancer progression and redox balance in human hepatocarcinoma (RNA-Seq)
ZNF706 belongs to a member of C2H2-type zinc finger proteins which exerts pivotal roles in cancer progression. However, the biological function and mechanism of ZNF706 are rarely investigated.   Using qRT-PCR and Western blot assays, we identified ZNF706 was frequently amplified in human hepatocarcinoma and high ZNF706 expression was associated with unfavorable HCC patient survival based on TCGA database. In vitro and in vivo experiments revealed that ZNF706 promoted HCC cell growth. Mechanistically, RNA-seq and ChIP-seq identified SLC7A11 was a critical target of ZNF706, and depletion of ZNF706 increased lipid peroxidation, cell death and decreased cystine uptake medicated by SLC7A11 contributing to redox homeostasis disruption. Furthermore, using luciferase report assays and ChIP-qPCR, we found MYC could regulate ZNF706 transcription by binding to ZNF706 promoter region, and further assay indicated MYC also involved in redox balance by modulating SLC7A11. Collectively, our study uncovers that the oncogenic role of ZNF706 in liver cancer, indicating that ZNF706 inhibition could be a potential treatment strategy for liver cancer. Overall design: To better determine the molecular mechanisms underlying ZNF706-modulated the biological process, we performed RNA-seq to explore the gene expression profiles using LM3 cells with stable ZNF706 knockdown or vector control and identified the DEGs