Duan-Bo Shi
Shandong University
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Duan-Bo Shi.
Oncotarget | 2015
Hai-Ting Liu; Ai-Yan Xing; Xu Chen; Ran-Ran Ma; Ya-Wen Wang; Duan-Bo Shi; Hui Zhang; Peng Li; Hong-Fang Chen; Yu-hong Li; Peng Gao
Vascular Endothelial Growth Factor C (VEGF-C) has critical roles in angiogenesis in human cancers; however, the underlying mechanisms regulating VEGF-C expression remain largely unknown. In the present study, VEGF-C protein expression and the density of blood vessels or lymphatic vessels were determined by immunohistochemistry in 103 cases of gastric cancer tissues. Suppression of VEGF-C by miR-27b, miR-101 and miR-128 was investigated by luciferase assays, Western blot and ELISA. The miRNAs expression levels were detected in human gastric cancers by real-time quantitative PCR. Cell proliferation, migration and invasion assays were performed to assess the effect of miRNAs on gastric cancer cells and human umbilical vascular endothelial cells (HUVECs). Our data showed that high VEGF-C expression was significantly associated with increased tumor size, advanced TNM classification and clinical stage, higher microvessel density (MVD) and lymphatic density (LVD), as well as poor survival in patients with gastric cancer. Furthermore, VEGF-C was found to be a direct target gene of miR-27b, miR-101, and miR-128. The expression levels of the three miRNAs were inversely correlated with MVD. Overexpression of miR-27b, miR-101, or miR-128 suppressed migration, proliferation activity, and tube formation in HUVECs by repressing VEGF-C secretion in gastric cancer cells. We conclude that miR-27b, miR-101 and miR-128 inhibit angiogenesis by down-regulating VEGF-C expression in gastric cancers.
The Journal of Pathology | 2016
Xu Chen; Ya-Wen Wang; Ai-Yan Xing; Shuai Xiang; Duan-Bo Shi; Lei Liu; Yan-Xiang Li; Peng Gao
Drug resistance is one of the major obstacles for improving the prognosis of breast cancer patients. Increasing evidence has linked the association of aberrantly expressed microRNAs (miRNAs) with tumour development and progression as well as chemoresistance. Despite recent advances, there is still little known about the potential role and mechanism of miRNAs in breast cancer chemoresistance. Here we describe that 16 miRNAs were found to be significantly down‐regulated and 11 up‐regulated in drug‐resistant breast cancer tissues compared with drug‐sensitive tissues, using a miRNA microarray. The results also showed miR‐489 to be one of the most down‐regulated miRNAs in drug‐resistant tissues and cell lines, as confirmed by miRNA microarray screening and real‐time quantitative PCR. A decrease in miR‐489 expression was associated with chemoresistance as well as lymph node metastasis, increased tumour size, advanced pTNM stage and poor prognosis in breast cancer. Functional analysis revealed that miR‐489 increased breast cancer chemosensitivity and inhibited cell proliferation, migration and invasion, both in vitro and in vivo. Furthermore, SPIN1, VAV3, BCL2 and AKT3 were found to be direct targets of miR‐489. SPIN1 was significantly elevated in drug‐resistant and metastatic breast cancer tissues and inversely correlated with miR‐489 expression. High expression of SPIN1 was associated with higher histological grade, lymph node metastasis, advanced pTNM stage and positive progesterone receptor (PR) status. Increased SPIN1 expression enhanced cell migration and invasion, inhibited apoptosis and partially antagonized the effects of miR‐489 in breast cancer. PIK3CA, AKT, CREB1 and BCL2 in the PI3K–Akt signalling pathway, demonstrated to be elevated in drug‐resistant breast cancer tissues, were identified as downstream effectors of SPIN1. It was further found that either inhibition of SPIN1 or overexpression of miR‐489 suppressed the PI3K–Akt signalling pathway. These data indicate that miR‐489 could reverse the chemoresistance of breast cancer via the PI3K–Akt pathway by targeting SPIN1. Copyright
PLOS ONE | 2014
Ya-Wen Wang; Duan-Bo Shi; Xu Chen; Chao Gao; Peng Gao
Accumulating evidence indicates that numerous microRNAs are involved in the tumorigenesis and progression of gastric cancer, while the clinical significance of microRNA-214 in gastric cancer is poorly understood and the exact role of microRNA-214 in gastric cancer remains obscure. In the present study, expression levels of microRNA-214 in 80 gastric carcinoma tissues, 18 nontumourous gastric tissues, and 4 types of gastric cancer cell lines were quantified by reverse transcription followed by real-time quantitative polymerase chain reaction (RT-qPCR), and the relationship between microRNA-214 expression and cliniopathological characteristics including prognosis was explored. To investigate the potential role of microRNA-214 in gastric cancer cell biological behaviour, we performed cell proliferation, apoptosis, migration and invasion assays in four gastric cancer cell lines and an immortalized gastric cell line in vitro. Our results showed that microRNA-214 was dramatically downregulated in gastric cancer tissues and gastric cancer cell lines, compared with nontumourous gastric tissues. Stepwise downregulation of microRNA-214 expression was observed among nontumourous gastric mucosa, nonmetastasis gastric cancer tissues, and metastasis gastric cancer tissues. The expression of microRNA-214 was significantly inversely correlated with lymph node metastasis and tumour size but had no correlation with the patients prognosis. Ectopic expression of microRNA-214 could inhibit cell migration and invasion ability in SGC7901 and MKN45 gastric cancer cells. And knockdown of microRNA-214 significantly facilitated cell proliferation, migration and invasion in a cell-specific manner in MKN28, BGC823 and GES-1 cells. Colony stimulating factor 1 (CSF1) was identified as a target gene of microRNA-214. In summary, our data demonstrated that microRNA-214 is a promising novel biomarker for lymph node metastasis in patients with gastric cancer. And we identified that downregulation of microRNA-214 may regulate the proliferation, invasion and migration of gastric cancer cells by directly targeting CSF1.
Cancer Letters | 2015
Duan-Bo Shi; Ya-Wen Wang; Ai-Yan Xing; Ji-Wei Gao; Hui Zhang; Xiang-Yu Guo; Peng Gao
MicroRNAs have been reported to play key roles in various human cancers, including gastric cancer. However, understanding of the expression of miR-100 and its regulatory mechanisms in human gastric cancer remains elusive. In this study, we reveal that miR-100 is downregulated in gastric cancer samples and gastric cancer cell lines. Furthermore, lower miR-100 expression was found in primary gastric cancer samples with lymphatic metastasis compared to those without lymphatic metastasis. Overexpression of miR-100 suppressed tumor growth in vivo and inhibited gastric cancer invasion and metastasis in vitro and in vivo. Furthermore, we demonstrated that miR-100 reduced gastric cancer aggressiveness by directly targeting ZBTB7A. Knockdown of ZBTB7A by siRNA disrupted gastric cancer progression by impairing tumor invasion and metastasis. High expression of ZBTB7A was significantly correlated with poorer prognosis in gastric cancer patients. Our results also showed that the transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) could induce the expression of miR-100 by binding to the putative promoter region of miR-100. This study demonstrated that miR-100 could be induced by C/EBPα and may act as a tumor suppressor gene by inhibiting ZBTB7A.
Experimental and Molecular Pathology | 2013
Ai-Yan Xing; Duan-Bo Shi; Wei Liu; Xu Chen; Yanlin Sun; Xiao Wang; Jianping Zhang; Peng Gao
One of the main mechanisms for multidrug resistance (MDR) involves multidrug resistance gene 1 (MDR1) which encodes P-glycoprotein (Pgp). Pgp acts as a drug efflux pump and exports chemotherapeutic agents from cancer cells. Specific inhibition of Pgp expression by gene therapy is considered a well-respective strategy having less innate toxicities. At present, the investigation of DRz in reversal MDR is scarce. In the study, phosphorothioate DRz that targets to the translation initiation codon AUG was synthesized and transfected into breast cancer cells and leukemia cells with MDR phenotype. ASODN (antisense oligonucleotide) and ribozyme targets to the same region were also synthesized for comparison analysis. Alterations in MDR1 mRNA and Pgp were determined by RT-PCR, Northern blot, flow cytometry and Rh123 retention tests. Chemosensitivity of the treated cells was determined by MTT assay. The results showed that DRz could significantly suppress expression of MDR1 mRNA and inhibit synthesis of Pgp. The efflux activity of Pgp was inhibited accordingly. Chemosensitivity assay showed that a 21-fold reduction in drug resistance for Adriamycin and a 45-fold reduction in drug resistance for Vinblastine were found in the treated cells 36h after transfection. These data suggest that DRz targeted to the translation initiation codon AUG can reverse MDR phenotype in cancer cells and restore their chemosensitivity. Moreover, the reversal efficiency of DRz is better than that of ribozyme and ASODN targets to the same region of MDR1 mRNA.
The Journal of Pathology | 2015
Ai-Yan Xing; Ya-Wen Wang; Zhong-Xue Su; Duan-Bo Shi; Bin Wang; Peng Gao
Increasing evidence supports the association of catenin‐δ1 (CTNND1, p120ctn) with tumour development and progression. However, the mechanism and clinical significance of CTNND1 deregulation in gastric cancer remain unknown. The expression level and cellular localization of CTNND1 were determined by immunohistochemistry in 126 human gastric cancer and 50 non‐tumourous tissues. The cellular localization of CTNND1 and epithelial cadherin (E‐cadherin) were detected by immunofluorescence. Cell proliferation, apoptosis, migration and invasion assays were performed to assess the effect of CTNND1 cDNA or CTNND1 siRNA transfection on gastric cancer cells. Luciferase assay, western blot analysis and in vivo assays were used to determine whether CTNND1 could be regulated by miR‐145. The results demonstrate that the cytoplasmic localization of CTNND1 protein, rather than expression level, was indicative of higher clinical stage, positive lymph node metastasis and poorer prognosis in gastric cancers. CTNND1 could promote gastric cancer cell migration and invasion with little effect on cellular proliferation and apoptosis. CTNND1 was proved to be a direct target gene for miR‐145. Besides suppressing cytoplasmic CTNND1 expression, miR‐145 could recover the membranous localization of CTNND1 and E‐cadherin. We conclude that cytoplasmic CTNND1 can serve as an independent prognostic factor for patients with gastric cancers. MiR‐145 inhibits invasion of gastric cancer cells not only by down‐regulating cytoplasmic CTNND1 expression but also by inducing the translocation of CTNND1 and E‐cadherin from the cytoplasm to the cell membrane through down‐regulating N‐cadherin. Copyright
Scientific Reports | 2017
Hai-Ting Liu; Ya-Wen Wang; Ai-Yan Xing; Duan-Bo Shi; Hui Zhang; Xiang-Yu Guo; Jing Xu; Peng Gao
The occurrence of lymph node metastases (LNM) after endoscopic submucosal dissection (ESD) in patients with gastric cancer (GC) leads to poor prognosis. However, few biomarkers are available to predict LNM in GC patients. Thus, we measured expression of 6 cancer-related miRNAs using real-time RT-PCR in 102 GC samples that were randomized into a training set and a testing set (each, 51 cases). Using logistic regression, we identified 4-miRNA (miR-27b, miR-128, miR-100 and miR-214) signatures for predicting LNM in GC patients. Patients with high-risk scores for the 4-miRNA signature tended to have higher LNM than those with low-risk scores. Meanwhile, the ROC curve of the 4-miRNA signature was better for predicting LNM in GC patients. In addition, Cox regression analysis indicated that a 2-miRNA signature (miR-27b and miR-214) or a miR-214/N stage signature was predictive of survival for GC patients. This work describes a previously unrecognized 4-miRNA signature involved in LNM and a 2-miRNA signature or miR-214/N stage signature related to GC patients’ survival.
Journal of Cancer Research and Clinical Oncology | 2014
Ya-Wen Wang; Duan-Bo Shi; Ya-Min Liu; Yanlin Sun; Xu Chen; Shuai Xiang; Qiang Fu; Jun-Min Wei; Peng Gao
PurposeIncreasing evidences demonstrate that CD227 plays a crucial role in the development and progression of breast cancer. However, the function of CD227 in breast carcinoma was still controversial and the investigation on CD227 in Asian race was scarce.MethodsTo investigate the relationship between CD227 and tumor characteristics of breast carcinoma, CD227, estrogen receptor (ER), progesterone receptor (PR), Her2⁄neu and Ki-67 were detected by immunohistochemistry in a series of 227 patients. The Kaplan–Meier method and log-rank tests were used to estimate the correlation between CD227 expression and patients’ prognosis. Furthermore, in vitro invasion assay was performed to examine the effect of CD227 on the invasiveness of breast carcinoma cells after transfection with CD227 cDNA or antisense phosphorothioate oligodeoxynucleotides (ASODN) against CD227 mRNA.ResultsOur data demonstrate that the cytoplasm staining and high expression of CD227 were positively related to the aggressiveness of breast cancer. Both circumferential membrane staining and cytoplasm staining were associated with lymph node metastasis. Moreover, the cytoplasm staining and overexpression of CD227 were found to be related to Her-2/neu positivity, higher Ki-67 positivity and poorer survival of patients. We further demonstrated that the invasion ability of breast carcinoma cells could be enhanced or inhibited by CD227 cDNA or ASODN, respectively.ConclusionsWe conclude that the aberrant expression of CD227, especially cytoplasm staining could be predictive for tumor aggressiveness, lymph node metastasis, poorer outcome of patients with breast cancers. And CD227 could promote the invasion ability of breast cancer cells, suggesting a potential role of CD227 as an oncogene in breast carcinoma.
International Journal of Molecular Medicine | 2017
Xiaomei Li; Wenlou Liu; Xu Chen; Ya-Wen Wang; Duan-Bo Shi; Hui Zhang; Ran-Ran Ma; Hai-Ting Liu; Xiang-Yu Guo; Feng Hou; Ming Li; Peng Gao
Transmembrane protease serine 4 (TMPRSS4) is a novel type II transmembrane serine protease that is overexpressed in various types of human cancers and has an important function in cancer progression. However, there is a paucity of data available regarding the biological effects of TMPRSS4 on breast cancer (BC) cells and the underlying mechanisms. In this study, expression of TMPRSS4 in BC tissues was detected by immunohistochemistry. The relationship between TMPRSS4 expression and clinicopathological characteristics as well as prognosis was evaluated. The effects of TMPRSS4 on cell proliferation, migration and invasion were investigated in BC cell lines in vitro. Additionally, RT-qPCR and western blot analysis were used to determine the expressions of epithelial-mesenchymal transition (EMT) biomarkers and TMPRSS4 in BC cell lines. We found that TMPRSS4 was overexpressed in BC tissues and its expression level was closely correlated with tumor size, histological grade, lymph node metastasis, clinical stage as well as poor survival (all P<0.05) and could be recognized as an independent prognostic factor for BC patients. Overexpression of TMPRSS4 promoted the proliferation, migration and invasion of BC cells in vitro. Moreover, TMPRSS4 knockdown significantly enhanced the expression of E-cadherin and claudin-1 and inhibited the expression of vimentin and Slug, indicating suppression of EMT. Our results suggest that TMPRSS4 plays a crucial role in the progression of BC. Moreover, TMPRSS4 overexpression promoted the proliferation, invasion and migration of BC cells by possibly inducing EMT. To conclude, TMPRSS4 may be a potential therapeutic target for cancer treatment.
Experimental and Molecular Pathology | 2013
Ai-Yan Xing; Bin Wang; Duan-Bo Shi; Xiao‐Fang Zhang; Chao Gao; Xiu-Quan He; Wenjun Liu; Peng Gao