RESUMO
Activating transcription factor 2 (ATF2) is a tumor driver gene implicated in several human malignancies. This study aimed to determine the roles of ATF2 and its related molecules in the tumorigenesis of hepatocellular carcinoma (HCC). According to the Pan-cancer bioinformatics system, ATF2 is highly expressed in HCC. An increase in the expression of ATF2 was identified in clinically collected tumor tissues and procured HCC cells. The silencing of ATF2 reduced the viability, colony formation, invasion, and death resistance of HepG2 and SNU-398 cells in vitro. ATF2 promoted the transcription of Wolf-Hirschhorn syndrome candidate 1 (WHSC1) by binding to its promoter. WHSC1 further increased the expression of DNA topoisomerase II alpha (TOP2A) in HCC by inducing the dimethylation of histone H3 lysine 36 (H3K36me2) in the TOP2A promoter region. TOP2A activated the oncogenic PI3K/AKT signaling pathway. Further overexpression of WHSC1 activated the TOP2A/PI3K/AKT axis and restored the malignant behaviors of HCC cells suppressed by ATF2 silencing in vitro. In summary, this study demonstrated that, depending on WHSC1, ATF2 can activate the TOP2A/PI3K/AKT signaling cascade to promote the tumorigenesis of HCC. ATF2, WHSC1, and TOP2A may serve as potential targets in managing HCC.
Assuntos
Fator 2 Ativador da Transcrição , Carcinoma Hepatocelular , Neoplasias Hepáticas , Fator 2 Ativador da Transcrição/genética , Carcinogênese/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , DNA Topoisomerases Tipo II/genética , DNA Topoisomerases Tipo II/metabolismo , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Neoplasias Hepáticas/patologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismoRESUMO
BACKGROUND: Diabetic chronic kidney disease (CKD) has become the main cause of death in diabetic patients, but its pathogenesis has not yet been clear. OBJECTIVE: To investigate the effects of reduced glutathione (GSH) on oxidative stress (OS), angiogenesis factors and lymphocyte subsets in diabetic CKD patients. METHODS: A total of 130 subjects were retrospectively studied. The subjects were divided into the control group (45 cases), treatment group (45 cases, treated with reduced GSH), and a healthy control group (40 cases). The levels of superoxide dismutase (SOD), advanced oxidation protein products (AOPP), malondialdehyde (MDA), endostatin (ES), and vascular endothelial growth factor (VEGF), and the percentages of lymphocyte subsets were detected. RESULTS: After treatment, the indexes of OS and angiogenesis and the percentage of CD3- CD19+ B cells were obviously decreased, and the percentages of T cell subsets and natural killer (NK) cell subsets were markedly increased in the treatment group compared with the control group. AOPP was positively correlated with angiogenesis indexes, MDA and CD3- CD19+ B cells, and negatively correlated with SOD and other lymphocyte subsets. SOD was inversely associated with angiogenesis indexes and MDA, and positively associated with lymphocyte subsets. Moreover, MDA had a positive correlation with angiogenesis indexes, B and T cell subsets, and a negative correlation with NK cell subsets. AOPP, MDA, SOD, VEGF, CD3+ T cells, CD3+ CD8+ T cells, CD3- CDl6+ CD56+ NK cells, and CD3- CDl6+ CD56+ NK T cells were the risk factors of diabetic CKD. CONCLUSION: GSH could inhibit OS and abnormal angiogenesis, and improve cellular immune response in CKD patients.
Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Glutationa/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Estudos de Casos e Controles , Nefropatias Diabéticas/patologia , Feminino , Humanos , Subpopulações de Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Neovascularização Fisiológica , Estresse Oxidativo , Insuficiência Renal Crônica/patologia , Fatores de RiscoRESUMO
OBJECTIVE: To analyze the relation of plasma D-dimer levels and incidence of deep venous thrombosis after spinal surgery. METHODS: The clinical data of 63 patients underwent spinal surgery from October 2009 to October 2010 were retrospective analyzed. There were 40 males and 23 females with an average age of 48 years old(21 to 76) in operation. Operation levels of 15 cases were in cervical vertebrae, 4 cases were in thoracic vertebrae,and 44 cases were in lumbar vertebrae. Thirty patients with spinal fracture were caused by trauma and 33 patients without trauma, 11 patients combined with nerve injury. The patients were divided into two groups according to plasma D-dimer levels, more than or equal to 500 microg/L was D-dimer positive group and less than 500 microg/L was D-dimer negative group. Venous blood of all patients early morning with empty stomach were testd on admission, and at 2 h, 1 d, 2 d, 3 d, 4 d, 6 d, 8 d, 10 d, 15 d after operation,respectively. RESULTS: There was no statistically significant differences in sex, operative segments, implants, operative posture, age, bleed volume, body weight, peroperative D-dimer levels between two groups. After operation, plasma D-dimer of 19 patients were more than or equal to 500 microg/L, with persistent or progressive increasing. Two cases occurred deep venous thrombosis in D-dimer positive group, they respectively were found at 3 days and 8 days after operation. Both of them underwent posterior decompression and internal fixation. However,no deep venous thrombosis was found in D-dimer negative group. CONCLUSION: Postoperative D-dimer assay can effective predict deep venous thrombosis occurrence. D-dimer level more than or equal to 500 microg/L will be considered as a risk factor for deep venous thrombosis after spinal surgery.
