CXXC5 Is Associated With SIRT1 Containing Complex And Promotes Breast Cancer Cell Invasion

Objective Since the first zinc finger protein TFIIIA that contains a conservative amino acid sequence displaying with a tetrahedron structre was found in Xenopus by Miller in 1985,more and more proteins with similar structure motif,characterized by the coordinatetion of one or more zinc ions with cysteine and histidine residues in order to stabilize the fold,had been identified.Classically,the number and order of the residues were used to classify different types of zinc fingers.(e.g,Cys2His2,Cys4 and Cys 6),and the most common "fold groups" of zinc fingers are the Cys2His2-like ones Zinc figer proteins are involved in biological process,through coordinatition with particular chromatin regulator or complex to impact on transcription,ranging from proliferation,differentiation,and apoptosis to carcinogenesis and immune dysregulation.CXXC5,a Cys2His2 type of zinc finger proteins,has been linked to human acute myeloid leukemia malignant peripheral nerve sheath tumors and T cell development.Yet,whether CXXC5 dysregulation contributes to breast carcinogenesis and,if so,the underlying mechanism remains to be investigated.Methods Although CXXC5 is a highly conservative zinc finger protein,its biological function in breast cancer remains unknown..Through bioinformatics analysis of overall survival in patients suffered from breast cancer with different expression level of CXXC5 Then through LC-MS,can examined the interactional proteins of CXXC5.Then following the western blot and RT-PCR the influence of CXXC5 on Epithelial–mesenchymal transition(EMT)and invation of breast cancer cells was examined.First,we utileized bioinformatics analysis of overall survival in patients suffered from breast cancer with different expression level of CXXC5;Second,we utileized Flag-CXXC5 containing protein complexes purified from MCF-7 to subjected to mass spectrometry analysis;Third,co-immunoprecipitation assyas were employed to validaite the interaction of CXXC5 with proteins baited from immunopurification;Fourth,the influence of CXXC5 on Epithelial–mesenchymal transition(EMT)and invation of breast cancer cells was examined.Results This study revealed CXXC5 is associated with SIRT1 and CRL4 B complex.Moreover,we demonstrated that CXXC5 promotes EMT and invasion of breast cancer cells,and bioinformatics analysis indicated that the expression level of CXXC5 is negatively correlated with overall survival of breast cancer patients,supporting the notion that CXXC5 dysregulation is tightly associated with breast carcinogenesis.