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

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

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

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

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

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

OBJECTIVETo investigate the expression and clinical significance of GINS complex in colorectal cancer (CRC).

METHODSThe expression level of GINS complex including PSF1, PSF2, PSF3 and SLD5 in CRC specimens (n=76) were detected by real-time fluorescent quantitative polymerase chain reaction. The association of GINS complex with clinicopathological parameters and prognosis of CRC patients were analyzed.

RESULTSThe relative expression level of PSF1, PSF2, PSF3, and SLD5 mRNA in CRC tissues was 0.001 853±0.000 651, 0.007 757±0.004 260, 0.000 967±0.000 481 and 0.003 248±0.001 721, which was significantly higher than that in normal colorectal mucosa tissues (0.000 352±0.000 169, 0.002 951±0.001 216, 0.000 472±0.000 271, and 0.001 675±0.001 156) (all P<0.01). PSF1 mRNA expression was associated with tumor size (P<0.01), and PSF2 mRNA expression with age (P<0.05) and lymph node metastasis (P<0.05). No correlations between PSF3 mRNA expression and clinicopathological parameters were observed. SLD5 mRNA expression was associated with lymph node metastasis (P<0.01). Patients with high expression of PSF1, PSF2 and SLD5 had worse 5-year overall survival rate (57.1%, 54.3%, and 54.3%) than those with low expression (77.1%, 80.0%, and 80.0%) (all P<0.05). Multivariable Cox regression analysis indicated that PSF1 mRNA expression (P<0.05) was an independent factor associated with prognosis of colorectal cancer.

CONCLUSIONSOverexpression of GINS complex in CRC is associated with clinicopathological characteristics and prognosis of colorectal cancer. PSF1 expression is prognostic for CRC patients.

Adult ; Aged ; Aged, 80 and over ; Chromosomal Proteins, Non-Histone ; metabolism ; Colorectal Neoplasms ; diagnosis ; metabolism ; pathology ; DNA-Binding Proteins ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Prognosis

Mammalian cells are frequently at risk of DNA damage from both endogenous and exogenous sources. Accordingly, cells have evolved the DNA damage response (DDR) pathways to monitor and assure the integrity of their genome. In cells, the intact and effective DDR is essential for the maintenance of genomic stability and it acts as a critical barrier to suppress the development of cancer in humans. Two central kinases for the DDR pathway are ATM and ATR, which can phosphorylate and activate many downstream proteins for cell cycle arrest, DNA repair, or apoptosis if the damages are irreparable. In the last several years, we and others have made significant progress to this field by identifying BRIT1 (also known as MCPH1) as a novel key regulator in the DDR pathway. BRIT1 protein contains 3 breast cancer carboxyl terminal (BRCT) domains which are conserved in BRCA1, MDC1, 53BP1, and other important molecules involved in DNA damage signaling, DNA repair, and tumor suppression. Our in vitro studies revealed BRIT1 to be a chromatin-binding protein required for recruitment of many important DDR proteins (ATM, MDC1, NBS1, RAD51, BRCA2) to the DNA damage sites. We recently also generated the BRIT1 knockout mice and demonstrated its essential roles in homologous recombination DNA repair and in maintaining genomic stability in vivo. In humans, BRIT1 is located on chromosome 8p23.1, where loss of hetero-zigosity is very common in many types of cancer. In this review, we will summarize the novel roles of BRIT1 in DDR, describe the relationship of BRIT1 deficiency with cancer development, and also discuss the use of synthetic lethality approach to target cancers with HR defects due to BRIT1 deficiency.
Animals ; Chromosomal Proteins, Non-Histone/genetics/metabolism/*physiology ; DNA Damage/genetics/*physiology ; DNA Repair/genetics/*physiology ; Humans ; Mice ; Models, Biological ; Neoplasms/*genetics ; Nerve Tissue Proteins/genetics/metabolism/*physiology

Mammalian cells are frequently at risk of DNA damage from both endogenous and exogenous sources. Accordingly, cells have evolved the DNA damage response (DDR) pathways to monitor and assure the integrity of their genome. In cells, the intact and effective DDR is essential for the maintenance of genomic stability and it acts as a critical barrier to suppress the development of cancer in humans. Two central kinases for the DDR pathway are ATM and ATR, which can phosphorylate and activate many downstream proteins for cell cycle arrest, DNA repair, or apoptosis if the damages are irreparable. In the last several years, we and others have made significant progress to this field by identifying BRIT1 (also known as MCPH1) as a novel key regulator in the DDR pathway. BRIT1 protein contains 3 breast cancer carboxyl terminal (BRCT) domains which are conserved in BRCA1, MDC1, 53BP1, and other important molecules involved in DNA damage signaling, DNA repair, and tumor suppression. Our in vitro studies revealed BRIT1 to be a chromatin-binding protein required for recruitment of many important DDR proteins (ATM, MDC1, NBS1, RAD51, BRCA2) to the DNA damage sites. We recently also generated the BRIT1 knockout mice and demonstrated its essential roles in homologous recombination DNA repair and in maintaining genomic stability in vivo. In humans, BRIT1 is located on chromosome 8p23.1, where loss of hetero-zigosity is very common in many types of cancer. In this review, we will summarize the novel roles of BRIT1 in DDR, describe the relationship of BRIT1 deficiency with cancer development, and also discuss the use of synthetic lethality approach to target cancers with HR defects due to BRIT1 deficiency.
Animals ; Chromosomal Proteins, Non-Histone/genetics/metabolism/*physiology ; DNA Damage/genetics/*physiology ; DNA Repair/genetics/*physiology ; Humans ; Mice ; Models, Biological ; Neoplasms/*genetics ; Nerve Tissue Proteins/genetics/metabolism/*physiology