Humans ; Pancreatic Neoplasms/metabolism* ; Prognosis ; Adenosine Triphosphatases/metabolism* ; Chromosomal Proteins, Non-Histone/metabolism*

OBJECTIVE: To study the mechanism of Chinese herbal medicine Fuzheng Kang'ai Formula (, FZKA) on tumor microenvironment (TME). METHODS: CIBERSORTx was used for analysis of TME. Traditional Chinese Medicine Systems Pharmacology and Analysis Platform was applied to identify compounds-targets network and the Cancer Genome Atlas (TCGA) was employed to identify the differential expression genes (DEGs) between tumor and paracancerous tissues in lung adenocarcinoma (LUAD) from TCGA-LUAD. Additionally, DEGs with prognosis in LUAD was calculated by univariable and multivariate Cox regression. The core targets of FZKA were analyzed in lung adenocarcinoma TME. Protein-protein interaction database was employed to predict down-stream of target. Quantitative reverse transcription polymerase chain reaction was employed for biological experiment in A549, H1299 and PC9 cell lines. RESULTS: The active and resting mast cells were significantly associated with prognosis of LUAD (P<0.05). Of the targets, CCNA2 as an important target of FZKA (hazard ratio=1.41, 95% confidential interval: 1.01-2.01, P<0.05) was a prognostic target and significantly associated with mast cells. CCNA2 was positively correlated with mast cell activation and negatively correlated with mast cell resting state. BCL1L2, ACTL6A and ITGAV were down-stream of CCNA2, which were validated by qRT-PCR in A549 cell. CONCLUSION FZKA could directly bind to CCNA2 and inhibit tumor growth by regulating CCNA2 downstream genes and TME of NSCLC closely related to CCNA2.
Actins ; Adenocarcinoma of Lung/pathology* ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Chromosomal Proteins, Non-Histone ; DNA-Binding Proteins ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Lung Neoplasms/metabolism* ; Tumor Microenvironment

The transition from spermatogonia to spermatocytes and the initiation of meiosis are key steps in spermatogenesis and are precisely regulated by a plethora of proteins. However, the underlying molecular mechanism remains largely unknown. Here, we report that Src homology domain tyrosine phosphatase 2 (Shp2; encoded by the protein tyrosine phosphatase, nonreceptor type 11 [Ptpn11] gene) is abundant in spermatogonia but markedly decreases in meiotic spermatocytes. Conditional knockout of Shp2 in spermatogonia in mice using stimulated by retinoic acid gene 8 (Stra8)-cre enhanced spermatogonial differentiation and disturbed the meiotic process. Depletion of Shp2 in spermatogonia caused many meiotic spermatocytes to die; moreover, the surviving spermatocytes reached the leptotene stage early at postnatal day 9 (PN9) and the pachytene stage at PN11-13. In preleptotene spermatocytes, Shp2 deletion disrupted the expression of meiotic genes, such as disrupted meiotic cDNA 1 (Dmc1), DNA repair recombinase rad51 (Rad51), and structural maintenance of chromosome 3 (Smc3), and these deficiencies interrupted spermatocyte meiosis. In GC-1 cells cultured in vitro, Shp2 knockdown suppressed the retinoic acid (RA)-induced phosphorylation of extracellular-regulated protein kinase (Erk) and protein kinase B (Akt/PKB) and the expression of target genes such as synaptonemal complex protein 3 (Sycp3) and Dmc1. Together, these data suggest that Shp2 plays a crucial role in spermatogenesis by governing the transition from spermatogonia to spermatocytes and by mediating meiotic progression through regulating gene transcription, thus providing a potential treatment target for male infertility.
Animals ; Cell Cycle Proteins/genetics* ; Cell Line ; Cell Survival ; Chondroitin Sulfate Proteoglycans/genetics* ; Chromosomal Proteins, Non-Histone/genetics* ; Gene Expression Regulation ; Gene Knockdown Techniques ; Infertility, Male ; Male ; Meiosis/genetics* ; Mice ; Mice, Knockout ; Mice, Transgenic ; Phosphate-Binding Proteins/genetics* ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics* ; Rad51 Recombinase/genetics* ; Real-Time Polymerase Chain Reaction ; Spermatocytes/metabolism* ; Spermatogenesis/genetics* ; Spermatogonia/metabolism*

To explore the magnetic resonance imaging (MRI) characteristics of glioma with Brg/Brm-associated factor 53a (BAF53a) expression.
 Methods: A total of 121 patients with glioma was divided into a BAF53a high expression group (n=79) and a low expression group (n=42) according to the results of immunohistochemistry. Then the MRI characteristics, including lesion location, number, boundary, maximum diameter, peripheral edema, midline structure shift, homogeneity, cystic necrosis, hemorrhage, strengthening degree, ependymal strengthening, pia mater enhancement, deep white matter invasion and lesion across the midline (total 14 items), were analyzed.
 Results: The results showed that there were significance difference in lesion border, lesion edema, enhancement of the lesion, and deep white matter invasion between the 2 groups (all P<0.05).
 Conclusion: The MRI characteristics, such as lesion border, lesion edema degree, enhancement degree of the lesion and deep white matter invasion, might be associated with BAF53a expression in gliomas.
Actins ; metabolism ; Brain Neoplasms ; Chromosomal Proteins, Non-Histone ; metabolism ; DNA-Binding Proteins ; metabolism ; Glioma ; Humans ; Magnetic Resonance Imaging ; Necrosis

Animals ; Chromosomal Proteins, Non-Histone ; chemistry ; genetics ; metabolism ; Humans ; Models, Molecular ; Mutation ; Transcription Factors ; chemistry ; genetics ; metabolism

Animals ; Centromere ; metabolism ; Chromosomal Proteins, Non-Histone ; metabolism ; Mice ; Models, Molecular ; Synaptonemal Complex ; metabolism

Chromosomal Proteins, Non-Histone ; chemistry ; genetics ; metabolism ; HeLa Cells ; Histones ; chemistry ; genetics ; metabolism ; Humans ; Protein Domains

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.
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 ; metabolism

CCCTC-binding factor (CTCF) is a highly conserved zinc finger protein and is best known as a transcription factor. It can function as a transcriptional activator, a repressor or an insulator protein, blocking the communication between enhancers and promoters. CTCF can also recruit other transcription factors while bound to chromatin domain boundaries. The three-dimensional organization of the eukaryotic genome dictates its function, and CTCF serves as one of the core architectural proteins that help establish this organization. The mapping of CTCF-binding sites in diverse species has revealed that the genome is covered with CTCF-binding sites. Here we briefly describe the diverse roles of CTCF that contribute to genome organization and gene expression.
Animals ; Cell Cycle Proteins/metabolism ; Chromosomal Proteins, Non-Histone/metabolism ; *Gene Expression Regulation ; Genome ; Humans ; Protein Binding ; Protein Interaction Maps ; Repressor Proteins/analysis/*metabolism

The long-term storage of memory requires the finely tuned coordination of intracellular signaling with the transcriptional, translational and epigenetic regulations of gene expression. Among the epigenetic mechanisms, however, we know relatively little about the involvement of chromatin remodeling-dependent control of gene expression in cognitive brain functions, compared with our knowledge of other such mechanisms (for example, histone modifications and DNA methylation). A few recent studies have implicated the Brm/Brg-associated factor (BAF) chromatin-remodeling complex, a mammalian homolog of the yeast Swi/Snf complex, in neuronal structural/functional plasticity and memory formation. The BAF complex was previously known to have a critical role in neurodevelopment, but these recent findings indicate that it also contributes to both cognitive functions in the adult brain and human mental disorders characterized by intellectual disability. In this review, we provide a brief overview of the BAF complexes, introduce recent research findings that link their functions to memory formation, and speculate on the yet-unknown molecular mechanisms that may be relevant to these processes.
Actins/metabolism ; Animals ; *Chromatin Assembly and Disassembly ; Chromosomal Proteins, Non-Histone/metabolism ; DNA-Binding Proteins/metabolism ; Gene Expression Regulation ; Humans ; Learning ; *Memory ; Multiprotein Complexes/metabolism ; Neurons/*metabolism ; Protein Binding ; Signal Transduction ; Transcription Factors/*metabolism