Minhang District Central Hospital

Shanghai, China

Minhang District Central Hospital

Shanghai, China

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Wei Z.,Shanghai University | Chen X.,Minhang District Central Hospital | Chen J.,Shanghai University | Wang W.,Shanghai University | And 2 more authors.
Biochemical and Biophysical Research Communications | Year: 2013

Ras association domain family (RASSF) proteins are encoded by several tumor suppressor genes that are frequently silenced in human cancers. In this study, we investigated RASSF10 as a target of epigenetic inactivation and examined its functions as a tumor suppressor in gastric cancer. RASSF10 was silenced in six out of eight gastric cancer cell lines. Loss or downregulation of RASSF10 expression was associated with promoter hypermethylation, and could be restored by a demethylating agent. Overexpression of RASSF10 in gastric cancer cell lines (JRST, BGC823) suppressed cell growth and colony formation, and induced apoptosis, whereas RASSF10 depletion promoted cell growth. In xenograft animal experiments, RASSF10 overexpression effectively repressed tumor growth. Mechanistic investigations revealed that RASSF10 inhibited tumor growth by blocking activation of β-catenin and its downstream targets including c-Myc, cyclinD1, cyclinE1, peroxisome proliferator-activated receptor δ, transcription factor 4, transcription factor 1 and CD44. In conclusion, the results of this study provide insight into the role of RASSF10 as a novel functional tumor suppressor in gastric cancer through inhibition of the Wnt/β-catenin signaling pathway. © 2013 Elsevier Inc.


Feng L.,Minhang District Central Hospital | Xie Y.,Minhang District Central Hospital | Zhang H.,Minhang District Central Hospital | Wu Y.,Shanghai JiaoTong University
Medical Oncology | Year: 2012

MicroRNAs (miRNAs) have emerged as posttranscriptional regulators that are critically involved in the pathogenesis of a number of human cancers. Recently, cyclin-dependent kinase 6 (CDK6) is found to be up-regulated in several types of human tumors and has been implicated in cancer initiation and progression. We have identified miR-107 as a potential regulator of CDK6 expression. A bioinformatics search revealed a putative target site for miR-107 within the CDK6 3′ untranslated region. Expression of miR-107 in gastric cancer cell lines was found inversely correlated with CDK6 expression. miR-107 could significantly suppress CDK6 3′ UTR luciferase reporter activity, and this effect was not detectable when the putative 3′ UTR target site was mutated. Consistent with the results of the reporter assay, ectopic expression of miR-107 reduced both mRNA and protein expression levels of CDK6, inhibited proliferation, induced G1 cell cycle arrest, and blocked invasion of the gastric cancer cells. Our results suggest that miR-107 may have a tumor suppressor function by directly targeting CDK6 to inhibit the proliferation and invasion activities of gastric cancer cells. © Springer Science+Business Media, LLC 2011.


Feng L.,Minhang District Central Hospital | Xie Y.,Minhang District Central Hospital | Zhang H.,Minhang District Central Hospital | Wu Y.,Shanghai JiaoTong University
Biochemical and Biophysical Research Communications | Year: 2011

The expression of N-myc downstream-regulated gene 2 (NDRG2) is present in normal tissues but low or undetectable in various cancers and thus poses a potential tumor suppressor gene. However, the expression of NDRG2 in colorectal tissues remains unknown. Here, our results showed that NDRG2 was down-regulated in colorectal cancer compared to benign colorectal tissues by using immunohistochemical staining and semi-quantitative RT-PCR analyses. Bisulfite sequencing analysis showed that the reduced NDRG2 expression was accompanied by de novo DNA methylation at the NDRG2 promoter. We also found that microRNA-650 (miR-650) targets a homologous DNA region in the promoter region of the NDRG2 gene and represses its expression at the transcriptional level. Reporter assay with 3'untranslated region of NDRG2 cloned downstream of the luciferase gene showed reduced luciferase activity in the presence of miR-650, providing strong evidence that miR-650 is a direct regulator of NDRG2. In conclusion, these results suggest that NDRG2 expression is regulated by promoter methylation and miR-650 in human colorectal cancer cells, and endogenous small noncoding RNA induced control of transcription may be a potential system for expressional regulation in human colorectal cancer cells. © 2011 Elsevier Inc.


Qing P.,Minhang District Central Hospital | Han L.,Shanghai JiaoTong University | Bin L.,Rui Jin Hospital | Yan L.,Shanghai JiaoTong University | Ping W.X.,Minhang District Central Hospital
Journal of Cellular Biochemistry | Year: 2011

Human helicase-like transcription factor (HLTF) is a functional homologue of yeast Rad5 that regulates error-free replication through DNA lesions. HLTF promotes the Lys-63-linked polyubiquitination of proliferating cell nuclear antigen (PCNA) that is required for maintaining genomic stability. Here, we identified the deubiquitylating enzyme ubiquitin-specific protease 7 (USP7) as a novel regulator of HLTF stability. We found that USP7 interacted with and stabilized HLTF after genotoxic stress. Furthermore, USP7 mediated deubiquitination significantly prolonged the half-life of HLTF, which in turn increased PCNA polyubiquitination. More intriguingly, silencing of USP7 rendered A549 cells highly sensitive to DNA damage and over-expression of HLTF attenuated this sensitivity. Thus, our results delineate a previously unknown USP7-HLTF-PCNA molecular network controlling DNA damage response. © 2011 Wiley Periodicals, Inc.


Dong W.,Zhengzhou University | Feng L.,Minhang District Central Hospital | Xie Y.,Minhang District Central Hospital | Zhang H.,Minhang District Central Hospital | Wu Y.,Shanghai JiaoTong University
Cancer Science | Year: 2011

LMX1A is epigenetically inactivated in cervical cancer. However, the expression and methylation status of LMX1A in gastric cancer tissues remains unknown. In the present study, we found that the expression of LMX1A was significantly decreased in gastric cancer tissues compared with normal tissues. A statistically significant inverse association was found between the LMX1A methylation status and expression of LMX1A in tumor tissues (P=0.008). Restoration of LMX1A induced cell apoptosis and suppressed anchorage-independent growth, suggesting LMX1A may be a potential biomarker for gastric cancer. © 2010 Japanese Cancer Association.


Wang Q.-B.,Minhang District Central Hospital | Zhu H.,Fudan University | Liu H.-L.,Minhang District Central Hospital | Zhang B.,Minhang District Central Hospital | Zhang B.,Shanghai JiaoTong University
Hepatology | Year: 2012

A meta-analysis was performed to assess and compare the accuracies of magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI) for the staging of hepatic fibrosis. Online journal databases and a manual search from January 2000 to May 2011 were used. We identified 41 studies, but only 14 met the criteria to perform a meta-analysis assessing MRE (five trials) or DWI (10 trials). Fibrosis was categorized by redistribution into five stages according to histopathological description. A bivariate binomial model was used to combine the sensitivity and specificity and their 95% confidence intervals (CIs), from which diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and summary receiver operating characteristic (sROC) were derived to indicate the diagnostic accuracy of imaging modalities. With MRE, the sensitivity, specificity, DOR, PLR, NLR, and area under sROC curve (with 95% CIs) for staging F0 ~ F1 versus F2 ~ F4 and F0 ~ F2 versus F3 ~ F4 were 0.94 (0.81-0.98), 0.95 (0.87-0.98), 20 (7-57), 0.06 (0.02-0.22), 317 (55-1,796), 0.98 (0.97-0.99) and 0.92 (0.85-0.96), 0.96 (0.91-0.98), 21 (10-45), 0.08 (0.04-0.16), 251 (103-609), and 0.98 (0.96-0.99), respectively; and with DWI, these values were 0.77 (0.71-0.82), 0.78 (0.69-0.85), 3 (2-5), 0.30 (0.22-0.40), 12 (6-21), 0.83 (0.79-0.86) and 0.72 (0.60-0.81), 0.84 (0.77-0.89), 5 (3-7), 0.34 (0.23-0.50), 13 (6-29), and 0.86 (0.83-0.89), respectively. A z test demonstrated that MRE had a significantly higher accuracy than DWI in those indicators (P < 0.05). Conclusion: MRE is more reliable for staging hepatic fibrosis, compared with DWI, with a high combination of sensitivity, specificity, likelihood ratios, DOR, and area under sROC curve. © 2012 American Association for the Study of Liver Diseases.


Chen Q.-H.,Minhang District Central Hospital | Wang Q.-B.,Minhang District Central Hospital | Zhang B.,Shanghai JiaoTong University
Tumor Biology | Year: 2014

Common functional polymorphisms in the promoter region of microRNAs (miRNAs), based on multiple lines of evidence, might participate in transcriptional regulation and other biological processes, which interact to increase the risk of developing breast cancer. Since 2005, many studies have investigated the association between breast cancer risk and common single nucleotide polymorphisms (SNPs) in miRNAs. However, the findings of several meta-analyses are inconclusive or ambiguous. The aim of this Human Genome Epidemiology meta-analysis was to determine more precisely the relationship between common miRNA polymorphisms and breast cancer risk. Twelve case-control studies with a total of 7,170 breast cancer patients and 8,783 healthy controls were included. Eight SNPs in miRNA genes were examined. When all eligible studies were pooled in the metaanalysis, the miR-196a-2 rs11614913*T, miR-499 rs3746444*T, and miR-605 rs2043556*A alleles predicted a decreased risk of breast cancer among Asians, while not Caucasians. In addition, the miR-27a rs895919*C allele might be a protective factor for breast cancer among Caucasians. However, for the miR-146a rs2910164 (G>C), miR-149 rs2292832 (G>T), miR-373 rs12983273 (C>T), and miR-423 rs6505162 (C>A) polymorphisms, we failed to find any significant association with the risk of breast cancer in any genetic model. In conclusion, the current meta-analysis supports that the miR-196a-2 rs11614913*T, miR-499 rs3746444*T, miR-605 rs2043556*A, and miR-27a rs895919*C alleles might be protective factors for breast cancer.


Zhang P.,Minhang District Central Hospital | Lu Y.,Shanghai JiaoTong University | Yu D.,Minhang District Central Hospital | Zhang D.,Minhang District Central Hospital | Hu W.,Minhang District Central Hospital
Cellular Physiology and Biochemistry | Year: 2015

Background: Tumor necrosis factor receptor-associated protein 1 (TRAP1), an essential mitochondrial chaperone is induced in rat hearts following ischemia/reperfusion (I/R), but its role in myocardial I/R injury is unclear. The present study examined the function of TRAP1 in cardiomyocyte hypoxia/reoxygenation injury in vitro and myocardial I/R injury in vivo. Methods: HL-1 cardiomyocytes transfected with TRAP1 or vector were subjected to simulated I/R (SI/R) in vitro. Cell death and mitochondrial function were assessed. Wild type (WT) and TRAP1 knockout (TRAP1 KO) mice were subjected to cardiac I/R in vivo. The infarct size and myocardial apoptosis were determined. WT and TRAP1 KO cardiomyocytes were subjected to SI/R in vitro. Mitochondrial function was assessed. Results: TRAP1 overexpression protects HL-1 cardiomyocytes from SI/R-induced cell death in vitro. The reduced cell death was associated with decreased ROS generation, better-preserved mitochondrial ETC complex activity, membrane potential, and ATP production, as well as delayed mPTP opening. Loss of TRAP1 aggravates SI/R-induced mitochondrial damage in cardiomyocytes in vitro and myocardial I/R injury and apoptosis in vivo. Conclusion: The results of the present study show that TRAP1 provides cardioprotection against myocardial I/R by ameliorating mitochondrial dysfunction. © 2015 S. Karger AG, Basel.


Zhao J.,Minhang District Central Hospital | Wu H.,Minhang District Central Hospital | Zheng L.,Minhang District Central Hospital | Weng Y.,Minhang District Central Hospital | Mo Y.,Minhang District Central Hospital
Brain Research | Year: 2013

Background and purpose Recovery after stroke varies considerably between individuals. An abundance of evidence suggests that genetic factors contribute to stroke recovery. The aim of this study was to determine whether or not the BDNF G196A polymorphism independently influences the occurrence, severity, and 90-day functional outcome in Chinese patients with ischemic stroke (IS). Methods BDNF G196A genetic variants were investigated in 494 IS and 346 controls. Severity was assessed by the National Institutes of Health Stroke Scale at the time of admission. Three hundred and eight patients were assessed 90 days post-stroke using the Modified Rankin Scale to determine stroke outcome. Results We showed that a significant association existed between the BDNF G196A AA genotype and the occurrence of IS (P=0.021), even after adjustment for covariates (P=0.028). The AA genotype of the BDNF G196A was associated with a poor outcome of recovery 3 months after stroke onset (P=0.008) was a novel finding, independent of other known predictors of poor outcome (P=0.012). Conclusions The BDNF G196A polymorphism was significantly associated with the occurrence and long-term outcomes of IS, thus BDNF G196A may be used as a prognostic biomarker and therapeutic target in IS. © 2013 Elsevier B.V.


Tian H.,Fudan University | Huang P.,Fudan University | Zhao Z.,Fudan University | Tang W.,Fudan University | And 2 more authors.
Cellular Physiology and Biochemistry | Year: 2014

Background/Aims: Hypoxia promotes the progression and metastasis of hepatocellular carcinoma (HCC). Hypoxia inducible factor-α (HIF-lα) regulates the expression of various chemokines involved in tumor growth, angiogenesis and metastasis.Methods: The role of HIF-la in HCC tumor growth and invasion and the prognosis of patients with HCC was investigated in cell lines and patient samples. HIF-lα mRNA and protein levels were assessed by gRT-PCR and western blotting. Silencing of HIF-lα downregulated the expression of granulocyte chemotactic protein-2 (GCP-2)/CXCL6, a CXC ELR+ chemokine, in HCC cells, and a luciferase assay showed that HIF-lα binds to a hypoxia response element in the promoter of CXCL6 and regulates its transcription. Induction of HIF-lα by hypoxia promoted the migration and invasion of HCC cells in vitro, and this effect was suppressed by an anti-CXCL6 antibody.Results: HIF-la is upregulated in HCC cell lines and tissues and its effect on promoting invasion and metastasis is mediated by its direct interaction with the pro-angiogenic chemokine CXCL6. CXCL6 expression was associated with poor prognosis of HCC patients. αConclusion: HIF-lα promotes HCC progression and metastasis by upregulating CXCL6 transcription in HCC cells, providing a potential novel therapeutic target for the treatment of HCC. Copyright © 2014 S. Karger AG, Base.

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