Project description:ZNF750 controls epithelial homeostasis by regulating epidermal-differentiation genes, a role underscored by its pathogenic mutations in esophageal squamous cell cancers (SCCs). However, the precise role of ZNF750 in SCC cell biology remains unclear. In this study, we report that ZNF750 is exclusively deleted, mutated and underexpressed in human SCCs, and low ZNF750 expression is associated with poor survival. Restoration of wildtype, but not mutant ZNF750 protein uniquely inhibited the malignant phenotype of SCC cells both in vitro and in vivo. Notably, ZNF750 promoted the expression of a LncRNA (TINCR) which mediated both cancer-inhibition and differentiation-induction effects of ZNF750. In addition, ZNF750 potently suppressed cell migration by directly inhibiting the transactivation of LAMC2. Together, our findings characterize ZNF750 as a crucial SCC-specific suppressor and uncover its novel anticancer-associated functions. Gene expression profile in CaSki following ZNF750 overexpression was examined by microarray gene expression analysis. To explore genes regulated by ZNF750 in squamous cell carcinoma, total RNA was isolated in biologic duplicate from CaSki either with ectopic expression of GFP (as control) or ZNF750, and hybridized to Affymetrix HG-U133 2.0 Plus arrays.
Project description:ZNF750 controls epithelial homeostasis by regulating epidermal-differentiation genes, a role underscored by its pathogenic mutations in esophageal squamous cell cancers (SCCs). However, the precise role of ZNF750 in SCC cell biology remains unclear. In this study, we report that ZNF750 is exclusively deleted, mutated and underexpressed in human SCCs, and low ZNF750 expression is associated with poor survival. Restoration of wildtype, but not mutant ZNF750 protein uniquely inhibited the malignant phenotype of SCC cells both in vitro and in vivo. Notably, ZNF750 promoted the expression of a LncRNA (TINCR) which mediated both cancer-inhibition and differentiation-induction effects of ZNF750. In addition, ZNF750 potently suppressed cell migration by directly inhibiting the transactivation of LAMC2. Together, our findings characterize ZNF750 as a crucial SCC-specific suppressor and uncover its novel anticancer-associated functions. Gene expression profile in CaSki following ZNF750 overexpression was examined by microarray gene expression analysis.
Project description:ZNF750 controls epithelial homeostasis by regulating epidermal-differentiation genes, a role underscored by its pathogenic mutations in esophageal squamous cell cancers (SCCs). However, the precise role of ZNF750 in SCC cell biology remains unclear. In this study, we report that ZNF750 is exclusively deleted, mutated and underexpressed in human SCCs, and low ZNF750 expression is associated with poor survival. Restoration of wildtype, but not mutant ZNF750 protein uniquely inhibited the malignant phenotype of SCC cells both in vitro and in vivo. Notably, ZNF750 promoted the expression of a LncRNA (TINCR) which mediated both cancer-inhibition and differentiation-induction effects of ZNF750. In addition, ZNF750 potently suppressed cell migration by directly inhibiting the transactivation of LAMC2. Together, our findings characterize ZNF750 as a crucial SCC-specific suppressor and uncover its novel anticancer-associated functions. RNA expression profile in UMSCC1 following ZNF750 wildtype overexpressing was analyzed by RNA-Seq.
Project description:ZNF750 controls epithelial homeostasis by regulating epidermal-differentiation genes, a role underscored by its pathogenic mutations in esophageal squamous cell cancers (SCCs). However, the precise role of ZNF750 in SCC cell biology remains unclear. In this study, we report that ZNF750 is exclusively deleted, mutated and underexpressed in human SCCs, and low ZNF750 expression is associated with poor survival. Restoration of wildtype, but not mutant ZNF750 protein uniquely inhibited the malignant phenotype of SCC cells both in vitro and in vivo. Notably, ZNF750 promoted the expression of a LncRNA (TINCR) which mediated both cancer-inhibition and differentiation-induction effects of ZNF750. In addition, ZNF750 potently suppressed cell migration by directly inhibiting the transactivation of LAMC2. Together, our findings characterize ZNF750 as a crucial SCC-specific suppressor and uncover its novel anticancer-associated functions.
Project description:Background: Zinc-finger protein 750 (ZNF750) is a potential tumor suppressor in oral squamous cell carcinoma (OSCC). However, the molecular mechanisms underlying its anti-tumor effect remain elusive in OSCC. We report the application of RNA sequencing to identify differentially expressed genes (DEGs) between vector groups and ZNF750 groups (over-expressed ZNF750 in CAL-27 cell), and to elucidate the genes and pathways involved in tumor suppression following the ZNF750 over-expression in OSCC cell line CAL-27 cell. Methods: The RNA sequence libraries were constructed, and the data were analyzed to identify DEGs between vector groups and ZNF750 groups. QPCR and western-blot was used to validate differential expression of candidate genes with cell cycle regulation. The cell cycle distribution was analyzed by BrdU staining. Results: By RNA sequencing profiling, 7,131 genes were differentially expressed in ZNF750 groups. Among the DEGs, 3,285 genes were upregulated, 3,846 genes were downregulated and 4,507 genes were identified in three main categories (cellular_component, biological process and molecular function) based on the gene ontology (GO) classification. The Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis defined the DEGs could be categorized into 280 pathways and identified the top two most significant pathways involved in spliceosome and cell cycle. Functional categorization and enrichment analysis revealed that most of DEGs involved in binding and catalytic activity, and the cell cycle associated genes was significantly enriched in response to ZNF750 over-expression. ZNF750 induced cell cycle arrest in G0/G1 phase of the cell cycle. Conclusion: Data from this study revealed that the cell cycle pathway was a key factor involved in the anti-tumor effect of ZNF750 in CAL-27 cells.
Project description:Transcriptional profiling of human cervical squamous cell carcinoma cell line CaSki comparing adherent cultured cells with spheres cultured in serum free culture medium. Goal was to identify candidate antigens for immunotherapy targeting cancer stem cells. Two-condition experiment, CaSki vs. CaSki-sphere cells.
Project description:Transcriptional profiling of human cervical squamous cell carcinoma cell line CaSki comparing adherent cultured cells with spheres cultured in serum free culture medium. Goal was to identify candidate antigens for immunotherapy targeting cancer stem cells.