Ziwei Wang

Chongqing Medical University, Ch’ung-ch’ing-shih, Chongqing Shi, China

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Publications (13)33.59 Total impact

  • Hui Li · Ziwei Wang · Wei Zhang · Kun Qian · Wei Xu · Shou Ru Zhang
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    ABSTRACT: F-box and WD repeat domain-containing7 (Fbxw7), a member of the F-box family of proteins, which are components of an E3 ubiquitin ligase complex, plays an important role as a general tumor suppressor in regulating the effects of various oncoproteins. Recently, accumulating studies have shown that Fbxw7 plays an important role in tumor cell motility, invasion and cancer metastasis. However, little is known about the signaling mechanisms that regulate tumor apoptosis, growth arrest and the epithelial -to-mesenchymal transition (EMT) in gastric cancer. In our study, we confirmed that Fbxw7 expression was decreased in gastric cancer tissues, and that Fbxw7 inhibited gastric cancer progression by inducing apoptosis and growth arrest. Furthermore, gastric cancer migration and invasion were decreased or increased following Fbxw7 overexpression or knockdown, respectively, and the expression of various EMT markers, such as E-cadherin, N-cadherin and vimentin were altered after Fbxw7 inhibition or overexpression. Furthermore, we demonstrated that Fbxw7 inhibits the EMT via the down-regulation of Snail 1 and ZEB 1, which are upstream transcription factors that promote this process. Additionally, RhoA showed higher expression in the same gastric cancer tissues than in normal tumor-adjacent samples. We found that Fbxw7 expression was negatively correlated with RhoA protein expression in gastric cancer tissues based on Pearson's correlation coefficient analysis. Moreover, we found that RhoA protein abundance was regulated by Fbxw7 via ubiquitination and proteasomal degradation in gastric cancer. We further demonstrated the effects of RhoA re-expression or inhibition on stable Fbxw7-overexpressing or Fbxw7-silenced cell lines in vitro and in vivo. These results suggest that Fbxw7 induces apoptosis and growth arrest and inhibits the EMT in part by down-regulating the RhoA signaling pathway.
    No preview · Article · Oct 2015 · Cancer letters
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    ABSTRACT: Current lack of recognition of normal gastric regional lymph nodes (GRLNs) and inherent defect of morphological imaging limit the accuracy of preoperative nodal (N) staging of gastric cancer. To map the distribution of normal GRLNs and evaluating the characteristics of GRLNs with diffusion-weighted imaging (DWI) in healthy population. Forty-nine enrolled healthy volunteers were divided into two age groups and underwent conventional magnetic resonance imaging (MRI) and DWI examinations. The characteristics of GRLNs in 14 regional stations, including short axis diameter (SD), short-to-long axis diameter ratio (SLR), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC), were recorded and compared between age groups and among different stations. The normal GRLNs were mainly distributed in station 7 in both age groups, followed by stations 3, 8, and 9. The SLR was lower in the young group than in the old group (P = 0.034) while SD, SNR, CNR, and ADC were significantly higher in the young group compared to the old group, P = 0.045, 0.041, 0.037, and 0.042, respectively. SD was different among stations in both age groups (P = 0.002, 0.001), especially bigger in station 8, and the SNRs and CNRs of stations 8 and 9 were relatively high in the old group (P = 0.031, 0.035), while there was no difference in ADC value. Better understanding of the appearances of normal GRLNs on conventional MRI and DWI may help to build more appropriate imaging criteria for GRLN assessment in gastric cancer. © The Foundation Acta Radiologica 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
    No preview · Article · Mar 2015 · Acta Radiologica
  • Hui Li · Ziwei Wang · Wei Zhang · Kun Qian · Gang Liao · Wei Xu · Shouru Zhang
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    ABSTRACT: VGLL4 is a member of the Vestigial-like proteins that functions as a tumor suppressor, which directly competes with YAP for binding TEADs in several cancer types. Recently, an increasing number of studies have reported that VGLL4 acts as a crucial role in regulating cell mobility, migration, and invasion. However, little is known about the signaling mechanisms in regulating epithelial-mesenchymal transition (EMT) of gastric cancer. In our study, we confirmed that the expression level of VGLL4 was down-regulated in gastric cancer tissues, and reduced VGLL4 expression levels inhibited apoptosis and promoted proliferation, migration, and invasion. Additionally, we found a phenomenon that VGLL4 was associated with the change in nuclear location of β-catenin, which suggested that β-catenin was a significant downstream factor of VGLL4. These results suggest that VGLL4 suppressed EMT in part via negative regulation of Wnt/β-catenin signaling pathway. Taken together, our study demonstrated that VGLL4 is important in the process of suppressing tumor progression of gastric cancer and provided a potential therapeutic strategy for gastric cancer.
    No preview · Article · Mar 2015 · Medical Oncology
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    ABSTRACT: Cyclin-dependent kinase 8 (CDK8), a gene encoding the cyclin-dependent kinase (CDK) component of the Mediator complex, is known as a colon cancer oncogene. Our recent study showed that CDK8 plays an important role in the formation of pancreatic cancer, but the CDK8 expression levels were not completely identical in different pancreatic cancer samples. The level of CDK8 expression depended on whether the K-ras gene was mutated; its expression was much higher in samples carrying a K-ras mutation than in wild-type K-ras samples. Moreover, CDK8 expression was reduced following mutated K-ras knockdown in K-ras-mutated pancreatic cancer cells, whereas CDK8 expression was increased following expression of mutated K-ras in wild-type K-ras cells. Our study demonstrates that mutated K-ras stimulates CDK8 expression, possibly by regulating HIF-1α, and both CDK8 and mutated K-ras were confirmed to promote cell proliferation and prevent apoptosis in vitro. Additionally, we found that both CDK8 and mutated K-ras promote the invasion and migration of pancreatic cancer cells via the positive regulation of the Wnt/β-catenin signaling pathway, thereby increasing the expression of Snail1 and ZEB1, which act as important stimulating factors of the epithelial-to-mesenchymal transition (EMT). Finally, knockdown of either CDK8 or mutated K-ras contributed to attenuated pancreatic cancer growth in BALB/c nude mice. In conclusion, these findings demonstrate that mutated K-ras promotes CDK8 expression and that the regulatory effects of CDK8 on the EMT are partially attributed to the Wnt/β-catenin signaling pathway.
    No preview · Article · Oct 2014 · Cancer Letters
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    Xuan Chen · Zhen Huang · Wenhua Ran · Gang Liao · Lang Zha · Ziwei Wang
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    ABSTRACT: Type 2 diabetes mellitus (T2DM) is a prevalent disease worldwide and during its conventional treatment, vascular complications remain unavoidable. Roux-en-Y gastric bypass (GBP) is able to induce the remission of T2DM. However, studies of duodenal-jejunal bypass (DJB), a modified procedure of GBP, are being carried out to investigate its ability to induce the remission of T2DM and protect the aorta from atherosclerosis. The present study aimed to investigate the effect of DJB on the rate of T2DM remission and the prevention of atherosclerosis in the aorta in rats with streptozotocin-induced diabetes without obesity, and to explore the mechanism of DJB in protecting the aorta from atherosclerosis. A T2DM rat model was established with a high-fat diet and low-dose streptozotocin. Surgery was performed to analyze its effects on glucose homeostasis, lipid metabolism, inflammation and pathological changes. Furthermore, changes in c-jun NH2-terminal kinase 1 (JNK1) and inhibitor of κB kinase (IKKβ) genes in the aorta following DJB surgery were examined. Levels of blood glucose, lipids, insulin and tumor necrosis factor (TNF)-α were significantly elevated in the T2DM diabetic model compared with the non-diabetic control. A gradual recovery was observed in the DJB group following surgery. Foam cells and atherosclerotic plaques appeared in the ascending aortic tissue in the sham-surgery and T2DM groups, whereas only slight lesions were observed in the DJB group. The expression levels of JNK1 and IKKβ genes in the aorta were significantly increased in the sham-operated and T2DM groups compared with those in the DJB and normal control groups. The present study demonstrated that DJB caused remission of T2DM without weight loss in non-obese rats. Thus, DJB may delay or prevent the occurrence and development of atherosclerosis in the aorta and this may occur through the JNK1 and nuclear factor κB (NF-κB) signaling pathways.
    Preview · Article · Sep 2014 · Experimental and therapeutic medicine
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    ABSTRACT: High mobility group protein A2 (HMGA2) and octamer-binding transcription factor 4 (Oct4) are transcription factors that play major roles in the acquisition of cancer stemness phenotypes and tumorigenicity of malignant neoplasms. The aim of this study was to analyze the association between HMGA2 and Oct4 expression and various clinicopathologic features in gastric cancer patients including invasion, metastasis, and clinical prognosis, in addition to overall survival. Immunohistochemistry was performed to explore the expression of HMGA2 and Oct4 in 158 gastric cancer and surrounding non-tumor tissues. Moreover, HMGA2 and Oct4 mRNA and protein levels were also detected by qRT-PCR and Western blotting, respectively, in 86 clinical tissue specimens and various gastric epithelial cell lines (GES-1, SGC7901, MKN45, and MKN27). Finally, associations between HMGA2 and Oct4 expression and clinicopathological features were analyzed by Pearson correlation coefficient. Survival analysis was performed by univariate and multivariate analyses. Taken together, we found that HMGA2 and Oct4 expression was significantly higher in gastric cancer tissues compared with non-cancerous tissues (P < 0.01), and HMGA2 and Oct4 protein levels were significantly higher in poorly differentiated gastric cancer cell lines (MKN45), moderately differentiated cell lines (SGC7901), and well-differentiated cell lines (MKN28) compared with human immortalized gastric epithelial cell lines (GES-1) (P < 0.01). Elevated HMGA2 and Oct4 levels were significantly associated with poor clinical prognosis (P < 0.05). Further conclusion showed that coexpression of HMGA2 and Oct4 in gastric cancer correlated with tumor invasion, metastasis, and clinical prognosis and predicted an unfavorable clinical outcome. These transcription factors may represent useful biomarkers to identify patients at high risk of postoperative recurrence.
    No preview · Article · Aug 2014 · Medical Oncology
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    ABSTRACT: The aim of this study was to evaluate the expression and role of Grhl2 in gastric cancer. Immunohistochemistry was performed to explore the expression of Grhl2 in gastric cancer and surrounding non-tumor tissues. Moreover, the mRNA and protein expression level of Grhl2 in human immortalized gastric epithelial cell line GES-1 and four gastric cancer cell lines (MGC803, SGC7901, MKN45, HGC27) were detected by qRT-PCR and Western blotting, respectively. To further investigate the role of Grhl2 in gastric cancer as well as the potential mechanisms, SGC7901 cells were transfected with lentiviral constructs expressing Grhl2 or empty vector, and then proliferation and apoptosis of SGC7901 cells were evaluated by MTT assay and flow cytometry, respectively. Finally, the protein expression level of c-Myc and Bcl-2 was detected by Western blotting. Both mRNA and protein expression level of Grhl2 were significantly downregulated in gastric cancer. Exogenous Grhl2 transduced into SGC7901 cells significantly inhibited the proliferation and promoted apoptosis. Meanwhile, over-expression of Grhl2 decreased c-Myc and Bcl-2 protein expression level. Taken together, our results demonstrated that Grhl2 downregulated in gastric cancer and may function as a tumor suppressor and play an important role in the development and progression of gastric cancer. These results may provide a new clue for treatment for gastric cancer.
    No preview · Article · Dec 2013 · Medical Oncology
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    Yi Guo · Jiangyan Yin · Lang Zha · Ziwei Wang
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    ABSTRACT: Platelet-derived growth factor B (PDGF-B), a vital growth factor which can induce angiogenesis and epithelial-mesenchymal transition (EMT), is important in the metastasis of many tumors. However, the roles of PDGF-B in gastric carcinoma are largely unknown. We investigated the correlation between PDGF-B, PDGFR-β and E-cadherin expression with the clinical features of gastric carcinoma patients to evaluate the relationship between PDGF-B signaling, E-cadherin and metastasis of gastric carcinoma, the correlation between PDGF-B and E-cadherin expression to assess the roles of PDGF-B signaling in metastasis of gastric carcinoma.. We detected expressions of PDGF-B, PDGFR-β and E-cadherin in gastric carcinoma tissues and normal gastric mucosa tissues of 64 patients with gastric carcinoma who had undergone surgical resection, and investigated their relationships with clinical features and the relationships between PDGF-B and E-cadherin expression in gastric carcinoma. In surgical specimens, tumor cells expressed PDGF-B, and PDGFR-β was expressed by tumor stromal cells. E-cadherin was expressed by both tumor cells and normal gastric mucosa cells. Expressions of PDGF-B and PDGFR-β were increased in gastric carcinoma tissues (p < 0.05) and were positively correlated with the depth of cancer invasion, lymph node metastasis and TNM stage (p < 0.05). The expression of E-cadherin was reduced in gastric carcinoma tissues (p < 0.05) and was negatively correlated with the depth of cancer invasion, lymph node metastasis and TNM stage (p < 0.05). The correlation between PDGF-B and E-cadherin expression was negative (p < 0.05). Our data indicate that either the overexpression of PDGF-B and PDGFR-β or the underexpression of E-cadherin is correlated with cancer progression and lymphogenous metastasis of gastric carcinoma. The PDGF-B signal pathway might induce EMT by down-regulating expression of E-cadherin to promote metastasis of gastric carcinoma.
    Preview · Article · Apr 2013 · Contemporary Oncology / Wspólczesna Onkologia
  • Gang Liao · Ziwei Wang · Neng Zhang · Pujiang Dong
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    ABSTRACT: Abstract Epidermal growth factor receptor (EGFR) promotes proliferation of cancer cells. Dominant negative EGFR (DNEGFR) can block EGFR signal pathway by competing with endogenous EGFR for ligands. However, whether EGFR is overexpressed in gastric cancer and whether DNEGFR contributes to the inhibition of gastric cancer growth are not known. In this study, with the methods of immunohistochemistry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, cytoflowmetry, Terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick-end labeling assay and western blotting; we demonstrate that EGFR is expressed in 29 of 60 of human gastric cancer. In addition, DNEGFR induces G0/G1 arrest by decreasing expression of phosphorylated retinoblastoma protein, phosphorylated GSK-3β, cyclin D1, and by increasing expression of p21 and p27 in human gastric cancer cell lines SGC-7901 and NCI-N87. Finally, DNEGFR induces apoptosis in these cells. Our results indicate that DNFGFR may provide promising treatment strategy for a subgroup of human gastric cancers that express EGFR.
    No preview · Article · Mar 2013 · Cancer Biotherapy & Radiopharmaceuticals
  • Lang Zha · Jing Zhang · Weixue Tang · Neng Zhang · Miao He · Yi Guo · Ziwei Wang
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    ABSTRACT: Background The high mobility group protein A2 (HMGA2) is an architectural transcription factor that plays an important role in the development and progression of many malignant neoplasms. High expression of HMGA2 in gastric cancer correlates with invasiveness of cancer and is an independent prognostic factor. The reason for this might be HMGA2 promoting epithelial–mesenchymal transitions (EMT), which is the key process of metastasis for some underlying mechanisms. Aims This study was designed to test whether HMGA2 participates in the EMT and to further understand the underlying mechanisms of EMT promoted by HMGA2. Methods We examined the cell biology and molecular biology changes after overexpression and knockdown HMGA2 of gastric cancer cells in vitro and vivo. To further understand the underlying mechanisms of EMT promoted by HMGA2, based on our previous study, we examined the changes of target genes of HMGA2 after overexpression and knockdown HMGA2 of gastric cancer cells. Results The results indicated that overexpressing HMGA2 enabled enhancing the oncogenic properties of gastric epithelial origin cell in vitro and in vivo. Furthermore, our study showed that HMGA2 was able to elicit EMT and regulate several genes which are closely related to the Wnt/β-catenin pathway by directly binding to their promoter thereby activating the Wnt/β-catenin pathway. Conclusions The Wnt/β-catenin pathway activated by HMGA2 might be the underlying mechanism of EMT in gastric cancer cells.
    No preview · Article · Nov 2012 · Digestive Diseases and Sciences
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    ABSTRACT: Krüppel-like factor 4 (KLF4) is a zinc-finger protein that plays an important role in the progression of gastric carcinoma. The abnormal activation of β-catenin frequently occurs in gastric cancer and has been associated with the promotion of tumor growth, invasion and metastasis. However, the potential interaction between KLF4 and β-catenin during gastric cancer development is unknown. In this study, a lentiviral KLF4 expression vector was constructed and utilized to transfect the human gastric cancer cell lines, SGC-7901, BGC-823, MKN-28 and MKN-45. KLF4 and β-catenin expression levels were measured by quantitative real-time RT-PCR and western blot analysis. Cell proliferation, colony formation and invasive potential were determined in the KLF4-transfected gastric cancer cells. The expression of E-cadherin and matrix metallopeptidase 2 (MMP2) was determined by western blot analysis. The overexpression of KLF4 significantly inhibited the expression of β-catenin in the MKN-45 gastric cancer cells. The restored expression of KLF4 suppressed proliferation, colony formation and inhibited the invasion and metastatic properties of MKN-45 gastric cancer cells. Furthermore, the forced expression of KLF4 in gastric tumor cell lines restored E-cadherin expression and inhibited MMP2 expression. Consistent with the in vitro findings, the enforced expression of the KLF4 gene in MKN-45 gastric carcinoma cells by lentiviral vector-mediated gene transfer effectively suppressed tumor growth in vivo. Our results show that KLF4 inhibits β-catenin expression and regulates the β-catenin-mediated biological behaviors of gastric cancer cells. The modulation of KLF4 expression may represent a novel therapeutic approach for β-catenin-driven malignancies.
    Preview · Article · Mar 2012 · International Journal of Oncology
  • Lang Zha · Ziwei Wang · Weixue Tang · Neng Zhang · Gang Liao · Zhen Huang
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    ABSTRACT: High mobility group protein A2 (HMGA2) is an architectural transcription factor that plays an important role in development and progression of malignant neoplasias. Recently, some studies reported that HMGA2 is also implicated in epithelial-mesenchymal transitions (EMT) and cancer stem cells. But the underlying mechanisms of these conditions are poorly understood. Therefore, we established an EMT model of gastric carcinoma cells by overexpressing HMGA2 in vitro, then global mapping of HMGA2 potential transcription factor binding sites was identified by promoter microarray in these cells, and the date obtained from the microarrays were validated via chromatin immunoprecipitation-PCR (ChIP-PCR) and real-time PCR. HMGA2 potential target genes were classified in KEGG database and Gene Ontology (GO) analyses. To our knowledge, this is the first report on the genome-wide analysis of HMGA2 downstream direct targets, and these findings will be valuable in understanding the roles of HMGA2 in EMT.
    No preview · Article · Jan 2012 · Molecular and Cellular Biochemistry
  • Gang Liao · Ziwei Wang · Lin Zhao · Neng Zhang · Pujiang Dong
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    ABSTRACT: Epidermal growth factor receptor (EGFR) blockade is a promising therapeutic approach for gastric cancer overexpressing EGFR. EGFR, with a cytoplasmic domain substituted by enhanced green fluorescent protein (DNEGFR-EGFP), can act as a dominant negative mutant receptor to block the EGFR signaling pathway by competing with endogenous EGFR for ligands. The aim of this study was to investigate the effects of DNEGFR-EGFP on the growth, invasion and angiogenesis of human gastric cancer cells, and to elucidate the possible mechanisms behind them. Using multiple cellular and molecular approaches such as gene transfection, MTT, flow cytometry, Western blotting, ELISA, invasion and angiogenesis assays, we found that DNEGFR-EGFP led to G0/G1 arrest by down-regulating cyclin D1 and CDK2 and up-regulating p27, and repressed the invasion and angiogenesis of SGC-7901 cells by inhibiting them from secreting MMP-2, MMP-9 and VEGF. These results indicate that the EGFR blockade strategy (termed dominant negative strategy targeting EGFR) may serve as a promising therapy for the treatment of EGFR-overexpressed gastric cancer.
    No preview · Article · Mar 2010 · Molecular Medicine Reports