ABSTRACT
OBJECTIVES@#A study was conducted to investigate the molecular mechanism of chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) influencing the invasion and metastasis of tongue squamous cell carcinoma and to provide a new target for clinical inhibition of invasion and metastasis of tongue squamous cell carcinoma.@*METHODS@#Ualcan website was used to analyze the expression of CHD1L in normal epithelial tissue and primary head and neck squamous cell carcinoma and to analyze the effect of lymph node metastasis on the expression of CHD1L in tissues with head and neck squamous cell carcinoma. The relationship between CHD1L expression and the survival rate of patients with head and neck squamous cell carcinoma was tested by the GEPIA website. Western blot was used to quantify the levels of CHD1L protein in human tongue squamous cell carcinoma CAL27 and immortalized human skin keratinocyte cell HaCaT. After knocking down CAL27 in human tongue squamous cell carcinoma cells with an RNA interference plasmid, the cells were designated as SiCHD1L/CAL27 and Scr/CAL27. Western blot was utilized to detect the expression of CHD1L in each group of cells. The change in CAL27 cell proliferation ability was tested by EdU proliferation test after CHD1L knockdown. The change of cell migration ability of each group cells was tested through the wound healing assay. Western blot was used to detect epithelial-mesenchymal transition (EMT) marker E-cadherin and Vimentin protein expression levels.@*RESULTS@#Ualcan database showed that the expression of CHD1L in primary head and neck squamous cell carcinoma tissues was higher than in normal epithelial tissues and in head and neck squamous cell carcinoma tissues with lymph node metastasis. GEPIA website analysis showed that the overall survival rate of patients with head and neck squamous cell carcinoma with high expression of CHD1L was significantly lower than that of patients with low expression. Western blot results showed that CHD1L expression in human tongue squamous carcinoma cells CAL27 was higher than that of human normal skin cells HaCaT. CHD1L expression in SiCHD1L/CAL27 cells was much lower than that in Scr/CAL27 cells. Results of EdU proliferation experiments showed the significant reduction in the cell proliferation ability of the SiCHD1L/CAL27 cells. Results of the wound healing experiments showed the reduction in the migration capacity of the SiCHD1L/CAL27 cells. The expression of E-cadherin increased, whereas that of Vimentin decreased, in SiCHD1L/CAL27 cells.@*CONCLUSIONS@#CHD1L promoted the EMT, proliferation, migration, and invasion ability of tongue squamous cell carcinoma cells.
Subject(s)
Humans , Adenosine Triphosphatases , Carcinoma, Squamous Cell/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation , DNA Helicases , DNA-Binding Proteins , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms , Neoplasm Invasiveness/genetics , Tongue , Tongue Neoplasms/geneticsABSTRACT
Previous studies suggested that chromodomain helicase DNA-binding proteins (CHDs), including CHD 1-8, were associated with several human diseases and cancers including lymphoma, liver cancer, colorectal cancer, stomach cancer, etc. To date, little research on CHD 9 in human cancers has been reported. In this study, we assessed the prognostic value of CHD 9 in patients with colorectal cancer (CRC). We screened for CHD 9 expression using immunohistochemical analysis in 87 surgical CRC specimens and found that the expression was upregulated in 81.5% of the cases, while 7.4% were decreased; in the remaining 11.1% of the cases, levels were not altered. Kaplan-Meier analysis showed that patients with high CHD 9 expression had better prognosis than those with low CHD 9 expression (54.5 vs 32.1%, P=0.034). Subsequently, Cox multi-factor survival regression analysis revealed that expression of CHD 9 protein was an independent predictor for CRC, with a hazard ratio of 0.503 (P=0.028). In addition, we found that CHD 9 expression was positively correlated with MSH2 (rs=0.232, P=0.036). We speculated that CHD9 might be a putative tumor suppressor gene, and could inhibit the development of CRC by participating in DNA repair processes. Our findings suggest that CHD 9 could be a novel prognostic biomarker and a therapeutic target for CRC. Further studies are needed to detect the effect of CHD 9 on cellular function and the expression of mismatch repair genes.
Subject(s)
Humans , Male , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Transcription Factors/metabolism , Colorectal Neoplasms/metabolism , Biomarkers, Tumor/metabolism , DNA-Binding Proteins/metabolism , Prognosis , Transcription Factors/genetics , Immunohistochemistry , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , Trans-Activators , DNA Helicases , DNA-Binding Proteins/genetics , Kaplan-Meier Estimate , Neoplasm StagingABSTRACT
Autism spectrum disorder (ASD) is a series of neurodevelopmental disorder with a large genetic component. However, the pathogenic genes and molecular mechanisms of ASD have not been clearly defined. Recent technological advancements, such as next-generation sequencing, have led to the identification of certain loci that is responsible for the pathophysiology of ASD. Three functional pathways, such as chromatin remodeling, Wnt signaling and mitochondrial dysfunction are potentially involved in ASD. In this review, we will focus on recent studies of the involvement of Wnt signaling pathway components in ASD pathophysiology and related drugs used in ASD treatment.
Subject(s)
Autism Spectrum Disorder , Autistic Disorder , beta Catenin , Chromatin Assembly and Disassembly , Neurodevelopmental Disorders , Wnt Signaling PathwayABSTRACT
AIM: To explore the effects of chromodomain protein 8 (CBX8) on the proliferation and apoptosis of human glioma cells.METHODS: The expression of CBX8 in the tissues and cells was detected by Western blot and RT-qPCR.The overexpression (Flag-CBX8) and silencing (sh-CBX8) vectors of CBX8 were constructed and transfected into glioma T98G cells and U87MG cells.The cell proliferation was detected by MTT assay and BrdU staining.The cell apoptosis was analyzed by flow cytometry.The protein expression of Rb/E2F1 was detected by Western blot.RESULTS: Compared with normal brain tissues and astrocytes, the expression of CBX8 was increased in the glioma tissues and glioma cells.Overexpression of CBX8 promoted the cell proliferation, inhibited the cell apoptosis, and upregulated the protein levels of Rb/E2F1.On the contrary, silencing of CBX8 inhibited the cell proliferation, promoted the cell apoptosis, and decreased the protein levels of Rb/E2F1 in the T98G cells and U87MG cells.Moreover, the expression of cyclin D1 and Bcl-2/Bax ratio were reduced after transfection with sh-E2F1 in the T98G cells and U87MG cells.CONCLUSION: CBX8 may regulate the proliferation and apoptosis of glioma cells through Rb/E2F1 pathway.
ABSTRACT
MRG proteins are conserved during evolution in fungi, flies, mammals and plants, and they can exhibit diversified functions. The animal MRGs were found to form various complexes to activate gene expression. Plant MRG1/2 and MRG702 were reported to be involved in the regulation of flowering time via binding to H3K36me3-marked flowering genes. Herein, we determined the crystal structure of MRG701 chromodomain (MRG701). MRG701 forms a novel dimerization fold both in crystal and in solution. Moreover, we found that the dimerization of MRG chromodomains is conserved in green plants. Our findings may provide new insights into the mechanism of MRGs in regulation of gene expression in green plants.
Subject(s)
Amino Acid Sequence , Arabidopsis , Genetics , Metabolism , Arabidopsis Proteins , Chemistry , Genetics , Metabolism , Binding Sites , Chromosomal Proteins, Non-Histone , Chemistry , Genetics , Metabolism , Cloning, Molecular , Crystallography, X-Ray , Escherichia coli , Genetics , Metabolism , Gene Expression , Histones , Chemistry , Genetics , Metabolism , Models, Molecular , Oryza , Genetics , Metabolism , Peptides , Chemistry , Genetics , Metabolism , Protein Binding , Protein Interaction Domains and Motifs , Protein Isoforms , Chemistry , Genetics , Metabolism , Protein Multimerization , Protein Structure, Secondary , Recombinant Proteins , Chemistry , Genetics , Metabolism , Sequence Alignment , Sequence Homology, Amino Acid , Viridiplantae , Genetics , MetabolismABSTRACT
The conserved band-interband pattern is thought to reflect the looped-domain organization of insect polytene chromosomes. Previously, we have shown that the chromodomain protein Chriz and the zinc-finger protein Z4 are essentially required for the maintenance of polytene chromosome structure. Here we show that both proteins form a complex that recruits the JIL-1 kinase to polytene chromosomes, enabling local H3S10 phosphorylation of interband nucleosomal histones. Interband targeting domains were identified at the N-terminal regions of Chriz and Z4, and our data suggest partial cooperation of the complex with the BEAF boundary element protein in polytene and diploid cells. Reducing the core component Chriz by RNAi results in destabilization of the complex and a strong reduction of interband-specific histone H3S10 phosphorylation.