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Du R.,PLA Fourth Military Medical University | Xia L.,PLA Fourth Military Medical University | Sun S.,PLA Fourth Military Medical University | Lian Z.,Thomas Jefferson University | And 8 more authors.
Journal of Cellular and Molecular Medicine | Year: 2010

Upregulated gene 11 (URG11), a new gene upregulated by Heptatitis B Virus X protein (HBx), was previously shown to activate β-catenin and promote hepatocellular growth and tumourigenesis. Although the oncogenic role of URG11 in the development of hepatocellular carcinoma has been well documented, its relevance to other human malignancies and the underlying molecular mechanisms remain largely unknown. Here we reported a novel function of URG11 to promote gastric cancer growth and metastasis. URG11 was found to be highly expressed in gastric cancer tissues compared with adjacent nontumourous ones by immunohistochemical staining and western blot. Knockdown of URG11 expression by small interfering RNA (siRNA) effectively attenuated the proliferation, anchorage-independent growth, invasiveness and metastatic potential of gastric cancer cells. URG11 inhibition led to decreased expression of β-catenin and its nuclear accumulation in gastric cancer cells and extensive costaining between URG11 and β-catenin was observed in gastric cancer tissues. Transient transfection assays with the β-catenin promoter showed that it was inhibited by URG11-specific small inhibitory RNA. Moreover, suppression of endogenous URG11 expression results in decreased activation of β-catenin/TCF and its downstream effector genes, cyclinD1 and membrane type 1 matrix metallopeptidase (MT1-MMP), which are known to be involved in cell proliferation and invasion, respectively. Taken together, our data suggest that URG11 contributes to gastric cancer growth and metastasis at least partially through activation of β-catenin signalling pathway. These findings also propose a promising target for gene therapy in gastric cancer. © 2008 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. Source


Yang B.,Wuhan General Hospital of Guangzhou Command PLA | Su K.,Wuhan University | Gao J.,Wuhan General Hospital of Guangzhou Command PLA | Rao Z.,Wuhan General Hospital of Guangzhou Command PLA
Asian Pacific Journal of Cancer Prevention | Year: 2012

The purpose of this study was to evaluate expression and prognostic value of matrix metalloproteinase-7 (MMP-7) in colorectal cancer (CRC) patients. CRC tissues and corresponding distal normal mucosa tissues of 118 CRC patients were assessed by immunohistochemistry. Correlations between MMP-7 expression, patients' clinic pathological features, and overall survival rate were analyzed. We found that positive expression of MMP-7 in CRC tissues was significantly higher than that in distal normal mucosa (61.0% vs. 39.8%, p =0.001). Poor histological differentiation, advanced clinical stage and lymph node metastasis were significantly correlated with MMP-7 expression in CRC. The overall survival rate was significantly higher in the MMP-7 negative group than the positive group (Log-rank test= 9.957, p= 0.002). MMP-7 appeared as a significant independent prognostic factor through multivariate survival analysis. Collectively, we found MMP-7 expression to be correlated with progression and metastasis of CRC and thus could be used as a predictive marker of prognosis in CRC patients. Source


Wu L.,Wuhan General Hospital of Guangzhou Command PLA | Li H.-H.,Wuhan General Hospital of Guangzhou Command PLA | Wu Q.,Wuhan General Hospital of Guangzhou Command PLA | Miao S.,Huazhong University of Science and Technology | And 3 more authors.
Journal of Molecular Neuroscience | Year: 2015

Lipoxin A4 (LXA4), a potent antioxidant and anti-inflammation mediator, protects brains against cerebral ischemia/reperfusion (I/R) injury in vivo. However, few reports concern its function on astrocytes during cerebral I/R injury. The pathogenesis of cerebral I/R injury involves oxidative stress caused by reactive oxygen species (ROS). Upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) is generally considered to reduce oxidative stress. Nrf2 can induce heme oxygenase-1 (HO-1) expression and glutathione (GSH) release to combat increased oxidative stress. We investigated the effects of LXA4 on astrocytic cell damage, the production of ROS, and Nrf2 pathway, especially on HO-1 expression and GSH release in cultured cortical astrocytes exposed to oxygen-glucose deprivation (OGD)/recovery (OGDR) insults. Primary astrocytes were subjected to a 4-h OGD, followed by 8-h recovery. Cell viability, the production of ROS, and GSH release were measured. Furthermore, Nrf2, HO-1, and p62 expression levels were determined by Western blot. Moreover, Nrf2 location was studied by immunofluorescence staining. Treatment of LXA4 attenuates OGDR-induced cell damage and the production of ROS in a concentration-related manner. LXA4 induced Nrf2 expression and its nuclear translocation, as well as HO-1 expression and GSH release. Moreover, LXA4 induced the excess p62 accumulation. These results indicate that LXA4 can effectively protect against OGDR-induced cell damage in astrocytes, and activation of Nrf2 pathway to reduce oxidative stress may be involved in its protective effects. p62 accumulation induced by LXA4 may be closely related to Nrf2 activation. © 2015, Springer Science+Business Media New York. Source


Yang B.,Wuhan General Hospital of Guangzhou Command PLA | Gao J.,Wuhan General Hospital of Guangzhou Command PLA | Rao Z.,Wuhan General Hospital of Guangzhou Command PLA | Shen Q.,Hubei University
Scandinavian Journal of Clinical and Laboratory Investigation | Year: 2012

The purpose of this study was to evaluate the association of matrix metalloproteinase-13 (MMP-13) expression with clinicopathological features and prognosis in colorectal cancer (CRC) patients. CRC tissues and distal normal mucosa tissues of 158 CRC patients were detected by immunohistochemistry. The correlations between MMP-13 expression, the patients' clinicopathological features, and overall survival rate were analyzed. It was found that positive expression rate of MMP-13 in distal normal mucosa tissues was significantly lower than that in CRC tissues (36.7% vs 60.8%, p < 0.001). Poor histological differentiation, advanced clinical stage and lymph node metastasis were significantly correlated with the MMP-13 expression in CRC. The overall survival rate of the MMP-13-negative group was significantly higher than the positive group (Log-rank test12.452, p <0.001). Collectively, we found that MMP-13 was correlated with progression and metastasis of CRC and could be used as a prognostic marker in CRC. © 2012 Informa Healthcare. Source


Wu L.,Wuhan General Hospital of Guangzhou Command PLA | Liu Z.J.,Huazhong University of Science and Technology | Miao S.,Huazhong University of Science and Technology | Zou L.B.,Huazhong University of Science and Technology | And 5 more authors.
Neurological Research | Year: 2013

Objectives: Lipoxin A4 (LXA4) is a potent anti-inflammatory mediator that exerts a neuroprotective effect following cerebral ischaemia/reperfusion (I/R) injury. However, little is known about the underlying mechanisms. Upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) is generally considered to reduce cerebral I/R injury. Nuclear factor erythroid 2-related factor 2 can induce haeme oxygenase-1 (HO-1) and glutathione (GSH) expression to combat increased oxidative stress. The present study aimed to investigate the effects of Nrf2 signalling on LXA4-mediated neuroprotection. Methods: Adult male Sprague Dawley rats were subjected to 2-hour middle cerebral artery occlusion followed by 24-hour reperfusion. Rats were randomly divided into four groups: Sham, I/R, LXA4, and LXA4+butoxycarbonyl-Phe-Leu-Phe-Leu-Phe (Boc2) (all n = 24). Brain infarction was detected by 2,3,5-triphenyltetrazolium chloride staining. After 24 hours of reperfusion, Nrf2, HO-1, and p62 expression levels were determined by western blot, and GSH synthesis was assessed. Results: Lipoxin A4 effectively reduced infarct volumes and improved neurological scores. These effects were partially blocked by Boc2, a specific antagonist of the LXA4 receptor (ALXR). Lipoxin A4 induced Nrf2 expression and its nuclear translocation, as well as HO-1 expression and GSH synthesis; Boc2 did not block these effects. The excess p62 accumulation induced by LXA4 might be closely related to Nrf2 activation. Discussion: Overall, our data suggest that Nrf2 upregulation is involved in the neuroprotective effects of LXA4 and may be ALXR independent. © W. S. Maney & Son Ltd 2013. Source

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