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1.
Atsushi Shiozaki Daisuke Iitaka Daisuke Ichikawa Shingo Nakashima Hitoshi Fujiwara Kazuma Okamoto Takeshi Kubota Shuhei Komatsu Toshiyuki Kosuga Hiroki Takeshita Hiroki Shimizu Yoshito Nako Hisami Sasagawa Mitsuo Kishimoto Eigo Otsuji 《Journal of gastroenterology》2014,49(5):853-863
Background
xCT is a component of the cysteine/glutamate transporter, which plays a key role in glutathione synthesis. The objectives of the present study were to investigate the role of xCT in the regulation of genes involved in cell cycle progression and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC).Methods
xCT expression in human ESCC cell lines was analyzed by Western blotting and immunofluorescent staining. Knockdown experiments were conducted with xCT siRNA, and the effect on cell cycle was analyzed. The cells’ gene expression profiles were analyzed by microarray analysis. An immunohistochemical analysis of 70 primary tumor samples obtained from ESCC patients that had undergone esophagectomy was performed.Results
xCT was highly expressed in TE13 and KYSE170 cells. In these cells, the knockdown of xCT using siRNA inhibited G1-S phase progression. Microarray analysis identified 1652 genes whose expression levels in TE13 cells were altered by the knockdown of xCT. Pathway analysis showed that the top-ranked canonical pathway was the G1/S checkpoint regulation pathway, which involves TP53INP1, CDKN1A, CyclinD1/cdk4, and E2F5. Immunohistochemical staining showed that xCT is mainly found in the nuclei of carcinoma cells, and that its expression is an independent prognostic factor.Conclusions
These observations suggest that the expression of xCT in ESCC cells might affect the G1/S checkpoint and impact on the prognosis of ESCC patients. As a result, we have a deeper understanding of the role played by xCT as a mediator and/or biomarker in ESCC. 相似文献2.
Du Y Shi L Wang T Liu Z Wang Z 《Journal of cancer research and clinical oncology》2012,138(10):1759-1767
Background
Cancer stem cells are regarded as the origin of tumors that can proliferate, relapse, and metastasize. Nanog, with its capacity to maintain the pluripotency and regulate proliferation and prevent differentiation, is one of the most important core markers of cancer stem cells. Studying the role of Nanog in esophageal squamous cell carcinoma (ESCC), therefore, has important implications.Methods
In the present study, we first detected the expression of Nanog in the ESCC and cell lines by RT-PCR, immunofluorescence, and immunohistochemisty. Then, we used small interfering RNA (siRNA) to block Nanog expression while evaluating the effect of Nanog siRNA on cell apoptosis and the combined effects with Cisplatin in ESCC cell lines.Results
The results showed that both mRNA and protein-level Nanog are overexpressed in ESCC tissues compared with their normal counterparts, and the increased occurrence of Nanog expression was positively correlated with TNM stages and histopathological differentiation of ESCC patients (p?0.01). At the same time, Nanog siRNA efficiently decreased Nanog expression and induced cell apoptosis. Treatment with Nanog siRNA in combination with Cisplatin, therefore, enhanced chemosensitivity.Conclusion
The present study’s results suggest that detecting Nanog might be helpful for diagnosing ESCC, and Nanog siRNA combined with Cisplatin may be a feasible strategy to enhance the sensitivity of chemotherapy in patients with ESCC. 相似文献3.
Chun-Tao Liu Sheng-Tao Zhu Peng Li Yong-Jun Wang Hao Zhang Shu-Tian Zhang 《Digestive diseases and sciences》2013,58(5):1256-1263
Background
Heparin-binding growth factor signaling is involved in the pathogenesis and development of human cancers. It can be regulated by sulfation of cell-surface heparan sulfate proteoglycans (HSPG). SULF1 is a heparin-degrading endosulfatase which can modulate the sulfation of HSPGs.Aim
The purpose of this study was to elucidate the role of SULF1 in modulating proliferation and invasion of esophageal squamous cell carcinoma (ESCC) by decreasing heparin-binding growth factor signaling.Methods
We restored SULF1 expression in the ESCC cell line KYSE150, and examined the effects of SULF1 expression on the proliferation and invasion of KYSE150 cells. In addition, we investigated the expression of SULF1 in human ESCC tissues and analyzed the correlation of SULF1 expression with clinicopathologic characteristics of ESCC.Results
Our study shows that re-expression of SULF1 in ESCC cell line results in the downregulation of hepatocyte growth factor-mediated activation of MAPK pathways with a resultant decrease in cell invasiveness. Cell proliferation was also inhibited in SULF1-transfected KYSE150 cells. Immunohistochemical assays reveal that SULF1 is expressed in nearly half of the human ESCC tissues but not in normal esophageal epithelial cells. SULF1 expression in human ESCC tissues is negatively correlated with tumor size and tumor invasion.Conclusion
This study identified that SULF1 inhibits proliferation and invasion of ESCC by decreasing heparin-binding growth factor signaling and suggested that SULF1 plays an inhibiting role in the pathogenesis of ESCC. 相似文献4.
Pei Li Wei-Min Mao Zhi-Guo Zheng Zi-Ming Dong Zhi-Qiang Ling 《Digestive diseases and sciences》2013,58(12):3483-3493
Background and Aim
miR-21, a putative tumor oncomiR, is a frequently overexpressed miRNA in a variety of tumors. Because it targets tumor-suppressor genes it has been linked to tumor progression. In this study we investigated the role of miR-21 in esophageal squamous cell carcinoma (ESCC), and its possible mechanism.Methods
Expression of miR-21 was detected by stem–loop RT-PCR in tissue from 76 invasive ESCC at stage I–IV and in their corresponding para-cancerous histological normal tissues (PCHNT). Thirty endoscopic esophageal mucosal biopsy specimens from non-tumor patients were used as controls. Expression of PTEN in 76 paired ESCC and PCHNT was investigated by real-time RT-PCR and an immunohistochemical method, respectively. Paired tumor and PCHNT specimens of 20 ESCC cases were randomly selected for western blot analysis. The effect of miR-21 on PTEN expression was assessed in the ESCC cell line with an miR-21 inhibitor to reduce miR-21 expression. Furthermore, the roles of miR-21 in cell biology were analyzed by use of miR-21 inhibitor-transfected cells.Results
Stem–loop RT-PCR revealed miR-21 was significantly overexpressed in ESCC tissues and cell lines. Overexpression of miR-21 correlated with tumor status, lymph node metastasis, and clinical stage. We demonstrated that knockdown of miR-21 significantly increased expression of PTEN protein. Consequent PTEN expression reduced cell proliferation, invasion, and migration.Conclusions
Our findings suggest that miR-21 could be a potential oncomiR, probably by regulation of PTEN, and a novel prognostic factor for ESCC patients. 相似文献5.
Yohei Ozawa Yasuhiro Nakamura Fumiyoshi Fujishima Saulo J. A. Felizola Kenichiro Takeda Ken Ito Hiroshi Okamoto Takashi Kamei Go Miyata Noriaki Ohuchi Hironobu Sasano 《Esophagus》2014,11(4):223-230
Background
Esophageal squamous cell carcinoma (ESCC) is a highly malignant disease because of its aggressive biological behavior and metastatic potential. Although several molecular markers have been identified as prognostic factors and/or clinicopathological correlation for the patients of ESCC, it has not been established as the effective new treatment for ESCC patients yet. Hepatocyte growth factor (HGF) is a biomarker as known to promote cell proliferation, motility, and invasion in various human malignancies. But the correlation with cytoplasmic HGF and ESCC has been unclear in details.Methods
We studied the correlation of HGF expression in ESCC tumor cells from 83 ESCC patients who were operated in our hospital using immunohistochemistry.Results
High cytoplasmic HGF expression was detected in 50.6 % (42/83) of ESCC cases examined. HGF immunoreactivity was also focally detected in some cancer-associated fibroblasts. High HGF expression group was significantly correlated with lymph node metastasis (P = 0.029) and tumor differentiation (P = 0.018). Increased HGF immunoreactivity was also correlated with clinicopathological features associated with invasiveness of carcinoma cells (lymphatic invasion, venous invasion, distant metastasis, and pathological stage) but not with actual clinical outcome of the patients.Conclusions
Results of our present study indicated that HGF cytoplasmic expression in ESCC was associated with increased potential for lymph node metastasis and carcinoma differentiation. These findings indicated that endogenous HGF did play an important role in progression and invasion of ESCC via c-Met/HGF autocrine loop together with HGF paracrine mechanisms. 相似文献6.
Zhu S Li Y Mi L Zhang Y Zhang L Gong L Han X Yao L Lan M Chen Z Zhang W 《Digestive diseases and sciences》2011,56(12):3569-3576
Background
HAb18G/CD147 expression has been associated with many tumor invasion molecules, which play important roles in recurrence and poor differentiation of esophageal squamous cell carcinoma (ESCC). However, the clinical implications of HAb18G/CD147 in ESCC are still unclear.Aims
In this study, we clarified the clinical significance of HAb18G/CD147 and characterized the association between HAb18G/CD147 and tumor invasion in ESCC cases.Methods
Tumor tissues were obtained from 86 ESCC patients who underwent surgical resection between 2002 and 2005. All patients that had received previous therapy were excluded. ESCC tissues were analyzed by IHC using anti HAb18G/CD147 antibody. The expression of HAb18G/CD147 mRNA in esophageal cancer cell lines was analyzed by RT?CPCR.Results
HAb18G/CD147 was uniformly expressed in EC109 and EC871214 cell lines, but negatively expressed in EPC2, esophageal normal squamous cell line. HAb18G/CD147 mainly localized to the membrane of tumor cells in 84.9% of ESCC patients (64 out of 86 cases). Furthermore, we also found that higher HAb18G/CD147 expression levels significantly correlated with lymph node metastasis, depth of tumor invasion and differentiation (P < 0.05). But the expression levels of HAb18G/CD147 in lymph node metastatic tissues were almost equal to that in the primary tumor tissues. Furthermore, lymph node metastasis and expression of HAB18G/CD147 were independent prognostic indicators in ESCC.Conclusions
The expression of HAb18G/CD147 might be involved in the progression and survival of ESCC. Therefore, HAb18G/CD147 could be a clinical marker for the poor prognosis in ESCC patients and may also be a potentially therapeutic target to improve the progression of ESCC. 相似文献7.
Jianguo Zhang Xiaojing Yang Yuchan Wang Hui Shi Chengqi Guan Li Yao Xianting Huang Zongmei Ding Yuejiao Huang Huijie Wang Chun Cheng 《Digestive diseases and sciences》2013,58(7):2028-2037
Background
Increased expression of cyclinH (CCNH) and cyclin-dependent kinase 7 (CDK7) has a relationship with poor prognosis in most human cancers.Aim
Investigate the expression of CCNH and CDK7 in human esophageal squamous cell carcinoma (ESCC) and the effect of chemotherapy on their expression.Methods
Western blotting and immunohistochemistry were used to measure the expression of CCNH and CDK7 proteins in ESCC and adjacent normal tissue in 98 patients. We use Cell Counting Kit-8 and cell flow to analyze the effects of cisplatin and interference of CCNH and CDK7 in cell cycle process.Results
Immunohistochemical analysis showed that CCNH and CDK7 expression were significantly associated with unfavorable clinicopathologic variables. CCNH and CDK7 protein levels were elevated in ESCC tissues in comparison with adjacent normal tissues. Survival analysis revealed that CCNH and CDK7 overexpression were significantly associated with overall survival (P < 0.001). Cisplatin or interference of CCNH or CDK7 led cells to grow slowly. Overexpression of CCNH and CDK7 in TE1 cells can lead to resistance to cisplatin.Conclusions
We can conclude that CCNH and CDK7 may play an important role in the tumorigenesis and development of ESCC. CCNH and CDK7 expression affected the chemotherapy of tumor. 相似文献8.
Guanghui Xu Shanhong Tang Jianjun Yang Kang Chen Jianqin Kang Guohong Zhao Fan Feng Xuewen Yang Lina Zhao Qun Lu Li Sun Liu Hong Taiqian Gong Hongwei Zhang 《Digestive diseases and sciences》2013,58(7):1871-1879
Background
Our previous study showed that BMP7 revealed significantly higher levels in esophageal squamous cell carcinoma (ESCC) tissues with lymph node metastasis compared with non-lymph node metastasis, using gene expression profiling assays. The roles of BMP7 in ESCC is not fully understood.Aim
The aim of this study was to investigate the effect of BMP7 on lymph node metastasis of ESCC and to explore its potential mechanism.Methods
Expression of BMP7 in ESCC tissues was evaluated by immunohistochemistry. BMP7 were down-regulated by RNA interference. The protein and mRNA levels of BMP7 were detected by western blot and RT-PCR, respectively. High content screening and transwell assay were used to identify the metastatic ability of tumor cells.Results
Positivity of BMP7 staining was 57.5 % in the tissues of primary carcinoma with lymph node metastasis compared to tissues without lymph node metastasis, and expression of BMP7 was significantly higher in the cell lines with highly metastatic capacity than that in the cell lines without metastatic ability. Suppression of endogenous BMP7 expression by siRNA in the highly metastatic cell lines resulted in significant reduction in ability of cell migration and invasion in both in vitro and in vivo studies. In addition, inhibition of BMP7 by siRNA also leads to up-regulation of E-cadherin and down-regulation of MMP-9 in the highly metastatic cell lines.Conclusions
These findings indicate that BMP7 modulates the expression of E-cadherin and MMP-9, and by which mechanism it may regulate cell migration and metastasis of ESCCs. 相似文献9.
Po-Kuei Hsu Hsuan-Yu Chen Yi-Chen Yeh Chueh-Chuan Yen Yu-Chung Wu Chung-Ping Hsu Wen-Hu Hsu Teh-Ying Chou 《Journal of gastroenterology》2014,49(8):1231-1240
Background
The molecular and genetic changes underlying esophageal squamous cell carcinoma (ESCC) tumor formation and rapid progression are poorly understood. Using high-throughput data analysis, we examined molecular changes involved in ESCC pathogenesis and investigated their clinical relevance.Methods
Five independent microarray datasets were examined for differentially expressed genes and pathways. For validation, mRNA expression in tumor and matched normal tissues from 16 ESCC cases was examined by cDNA microarray, and protein expression in 97 ESCC specimens was investigated using immunohistochemical stains. The association between clinicopathological parameters and the expression of Aurora kinase A (Aurora-A) and TPX2 was analyzed. The impact of TPX2 expression was also assessed in ESCC cancer cells.Results
AURKA and TPX2, members of the “Role of Ran in mitotic spindle regulation” pathway, were selected for further investigation. Verification by cDNA microarray showed that both genes were overexpressed in tumor tissues, and immunohistochemical staining showed Aurora-A and TPX2 expression in 88.4 and 90.6 % of ESCC specimens, respectively. High TPX2 expression was a significant prognosticator for overall and disease-free survival in univariate analysis and remained an independent prognostic factor in multivariate analysis (HR 1.802, p = 0.037). TPX2 knockdown clones showed inhibited cellular proliferation in growth curve studies and formed fewer colonies in the clonogenic assay.Conclusions
Using bioinformatics resources, which were validated by microarray analysis and immunohistochemistry stains, and manipulation of TPX2 expression in ESCC cell lines, we demonstrated that TPX2 expression is associated with cell proliferation and poor prognosis among patients with resected ESCC. 相似文献10.
Chun-Mei Wang Qing-Quan Wu Su-Qing Li Fang-Jun Chen Lei Tuo Hai-Wei Xie Yu-Suo Tong Lv Ji Guo-Zhi Zhou Gang Cao Ming Wu Jin Lv Wei-Hong Shi Xiu-Feng Cao 《Digestive diseases and sciences》2014,59(3):591-597
Background
Recent studies revealed that long noncoding RNAs (lncRNAs) play critical regulatory roles in cancer biology. PlncRNA-1 is one of lncRNAs that is associated with cell apoptosis and proliferation of prostate cancer.Aim
This study aimed to assess the potential role of PlncRNA-1 in the pathogenesis of esophageal squamous cell carcinoma (ESCC).Materials and Methods
Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of PlncRNA-1 in 73 pairs of ESCC and their matched normal tissues. The correlation of PlncRNA-1 with clinicopathological features and clinical stages was also analyzed. Cancer cell proliferation and apoptosis were assessed following knock-down of PlncRNA-1 by MTT, colony formation assay, and flow cytometry.Results
The expression of PlncRNA-1 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (69.8 %, p < 0.05), and the high level of PlncRNA-1 expression was significantly correlated with advanced clinical stage (p < 0.01) and lymph node metastasis (p < 0.05). Furthermore, knockdown of PlncRNA-1 reduced cell proliferation and increased the apoptosis in vitro.Conclusions
PlncRNA-1 plays an important role in ESCC cell proliferation. Overexpression of PlncRNA-1 is correlated with advanced tumor stage and lymph node metastasis, and may serve as a potential prognostic marker and therapeutic target for ESCC. 相似文献11.
Cuihua Lu Jing Zhang Song He Chunhua Wan Aidong Shan Yingying Wang Litao Yu Guoliang Liu Ken Chen Jing Shi Yixin Zhang Runzhou Ni 《Digestive diseases and sciences》2013,58(9):2713-2720
Background
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide. It is important to understand molecular mechanisms of HCC progression and to develop clinically useful biomarkers for the disease.Aim
We aimed to investigate the possible involvement of α-tubulin1b (TUBA1B) in HCC pathology.Methods
Tissue specimens were obtained from 114 HCC patients during hepatectomy. Immunohistochemistry and western blot analysis were used to detect TUBA1B expression in HCC tissues and cell lines. TUBA1B was knocked down in HCC cells by siRNA transfection. CCK-8 assay and flow cytometry were applied to determine cell proliferation and cell cycle progression, respectively. The efficacy of paclitaxel chemotherapy was evaluated by plate colony formation assay.Results
TUBA1B was higher expressed in HCC tumor tissues than in adjacent nontumor tissues. TUBA1B and Ki-67 expressions were positively related to each other, and both their expressions were significantly associated with histological grade of HCC patients. Univariate and multivariate survival analyses revealed that TUBA1B was a significant predictor for overall survival of HCC patients. TUBA1B expression was increased in HCC cells during the G1- to S-phase transition. TUBA1B knockout in HCC cells inhibited cell proliferation, and attenuated resistance to paclitaxel.Conclusions
Our results indicated that TUBA1B expression was upregulated in HCC tumor tissues and proliferating HCC cells, and an increased TUBA1B expression was associated with poor overall survival and resistance to paclitaxel of HCC patients. 相似文献12.
Fujikawa H Tanaka K Toiyama Y Saigusa S Inoue Y Uchida K Kusunoki M 《Journal of gastroenterology》2012,47(7):775-784
Background
The neurotrophic receptor tropomyosin related kinase (TrkB) is associated with tumor progression in neuroblastoma and certain human malignancies. Recent reports indicate TrkB may participate in the epithelial–mesenchymal transition (EMT). This study investigates whether TrkB expression is associated with the clinical outcome of colorectal cancer (CRC) patients and whether TrkB induces EMT in CRC cells.Methods
TrkB and E-cadherin expression in surgical tissue samples and clinicopathological data from 102 CRC patients were analyzed by real-time polymerase chain reaction and immunohistochemistry. The biological role of TrkB in CRC was analyzed using RNA interference against TrkB in the CRC cell line SW480 to assess tumor progression and the correlation between TrkB and E-cadherin expression.Results
Patients with high TrkB mRNA expression in clinical samples had a significantly poorer prognosis relative to those with low TrkB levels (p?=?0.03). TrkB was inversely correlated with E-cadherin at both the mRNA and protein levels. In vitro, cell proliferation (p?=?0.02), migration (p?0.001), and invasion (p?0.001) were significantly inhibited by TrkB knockdown while the anoikis rate increased in TrkB siRNA-transfected cells compared to control siRNA. Interestingly, E-cadherin expression in TrkB siRNA-transfected cells was higher than in control cells and vimentin was lower conversely.Conclusions
High TrkB expression is associated with poor prognosis in CRC patients and enhanced malignant potential in terms of proliferation, migration, invasion, and anoikis inhibition in CRC cells. These results indicate TrkB could induce EMT and play an important role in CRC progression to metastasis. 相似文献13.
Lingling Chen Sujie Ni Mei Li Chaoyan Shen Zhipeng Lin Yu Ouyang Fei Xia Li Liang Wenyan Jiang Runzhou Ni Jianguo Zhang 《Digestive diseases and sciences》2017,62(2):387-395
Background
BCCIP was originally identified as a BRCA2 interacting protein in humans and Ustilago maydis. It had low expression in some human cancer tissues. However, recent research indicated that many caretaker genes are also necessary for cell viability and their expression could contribute to tumor progression.Aim
To characterize whether BCCIP is a caretaker gene in esophageal squamous cell carcinoma (ESCC).Methods
Western blotting and immunohistochemistry were used to measure the expression of BCCIP β. In vitro studies were used to verify the effects of BCCIP β in Eca109 cells.Results
Expression of BCCIP β was notably higher in tumor tissues of ESCC and Eca 109 cells. Meanwhile, the immunohistochemistry stain revealed that BCCIP β was positively correlated with clinical pathologic variables such as tumor size and tumor grade, as well as Ki-67, and prompted poor prognosis. In vitro studies such as starvation and refeeding assay along with BCCIP β-shRNA transfection assay demonstrated that BCCIP β expression promoted proliferation of ESCC cells. In addition, BCCIP β downregulation by silencing RNA significantly decreased the rate of colony formation, alleviated cellular apoptosis and increased the chemosensitivity of cisplatin.Conclusions
This research first put forward that BCCIP β is an oncogene in human ESCC and contributes to the poor outcome of the deadly disease.14.
Donglei Zhou Xun Jiang Weixing Ding Lijun Zheng Lei Yang Chengzhu Zheng Liesheng Lu 《Journal of cancer research and clinical oncology》2013,139(12):2057-2070
Purpose
This study aims to investigate the role of siRNA silencing fibroblast growth factor receptor (FGFR) expression in promoting chemotherapy effect of gastric cancer and to explore its mechanism.Methods
Human gastric cancer cells MGC80-3 were divided into four groups: control group, cisplatin group (2 μg/L), cisplatin (2 μg/L) + siRNA group and siRNA group. The expressions of FGFR in four groups were detected by immunofluorescence. The cell proliferation and apoptosis were detected by MTT assay and flow cytometry. The protein expression levels of vascular endothelial growth factor receptor (VEGFR), caspase-3 and Bax were detected by Western blot. Further, animal model of gastric cancer was established and divided into four groups as in vitro experiment. The expression of FGFR mRNA in tumor tissue was detected by the real-time fluorescence quantitative polymerase chain reaction. The size of tumor was measured to analyze the effects of treatment. Histopathological detections were performed by hematoxylin and eosin staining and immunohistochemistry.Results
For in vitro experiment, significant decrease inFGFR expression, inhibition of proliferation and promotion of apoptosis were observed in siRNA-treated cells, so as cisplatin group. siRNA also resulted in the reduction of VEGFR and rise in apoptosis-related protein (caspase-3). As for the experiment in vivo, siRNA also suppressed the expression of FGFR and enhanced tumor shrink. Furthermore, the co-administration of siRNA and cisplatin revealed a more excellent antitumor effect than other therapies.Conclusions
siRNA can effectively suppress FGFR expression and cell proliferation, but promote apoptosis in vitro and also inhibit tumor growth and FGFR production in vivo. siRNA-participated chemotherapy may provide an efficient therapeutic approach to treat gastric cancer. 相似文献15.
Purpose
To detect the expression levels of ubiquitin-specific protease 22 (USP22) in human esophageal squamous cell carcinoma (ESCC) and to correlate it with clinicopathologic and prognostic data.Methods
The immunoreactivity of USP22 protein was analyzed in 157 pathologically characterized ESCC tissues by immunohistochemistry. All statistical analyses were performed with SPSS statistical software to evaluate the association of USP22 protein with clinicopathologic factors and survival.Results
High expression of USP22 protein was detected in 50.96?% of 157 ESCC tissues and significantly associated with invasion depth, lymph node metastasis, pathologic stage and tumor relapse (P?0.05, respectively). Univariate survival analysis showed that patients with high expression of USP22 protein had a significantly poorer 5-year disease-specific survival (P?=?0.002), and multivariate survival analysis showed that high expression of USP22 protein was an independent prognosticator for unfavorable disease-specific survival (P?=?0.039). Further survival analysis stratified by pathologic stage demonstrated that high expression of USP22 protein significantly predicted unfavorable clinical outcome (P?=?0.029) among patients with pathologic stage IIb–III diseases.Conclusion
USP22 protein plays an essential role in ESCC progression and has clinical potentials not only as a promising biomarker to identify the subgroup of patients with more aggressive tumors and poor prognostic potential but also as an attractively therapeutic target for ESCC. 相似文献16.
Baofei Jiang Zengliang Li Wenjie Zhang Haixiao Wang Xiaofei Zhi Jin Feng Zheng Chen Yi Zhu Li Yang Hao Xu Zekuan Xu 《Journal of gastroenterology》2014,49(6):1011-1025
Background
Aquaporin-3 (AQP3) is a water transporting protein which plays an oncogenic role in several malignant tumors. However, its regulatory mechanism remains elusive to date. In this study, we investigated the microRNA-mediated gene repression mechanism involved in AQP3's role.Methods
The potential microRNAs targeting AQP3 were searched via bioinformatic methods and identified by luciferase reporter assays, microRNA RT–PCR and western blotting. The expression patterns of miR-874 and AQP3 in human gastric cancer (GC) specimens and cell lines were determined by microRNA RT-PCR and western blotting. 5-ethynyl-2′-deoxyuridine, cell migration and invasion assays and tumorigenicity in vivo were adopted to observe the effects of miR-874 depletion or ectopic miR-874 expression on GC cell phenotypes. Cell apoptosis was evaluated by FACS and TUNEL in vitro and in vivo respectively.Results
miR-874 suppressed AQP3 expression by binding to the 3′UTR of AQP3 mRNA in GC cells. miR-874 was significantly down-regulated and reversely correlated with AQP3 protein levels in clinical samples. Analysis of the clinicopathological significance showed that miR-874 and AQP3 were closely correlated with GC characteristics. Functional analyses indicated that ectopic miR-874 expression suppressed the growth, migration, invasion and tumorigenicity of GC cells, whereas miR-874 knockdown promoted these phenotypes. Down-regulation of Bcl-2, MT1-MMP, MMP-2 and MMP-9 and upregulation of caspase-3 activity and Bax were involved in miR-874 inducing cell apoptosis, and inhibiting migration and invasion.Conclusions
These results provide a mechanism by which AQP3 is upregulated, as well as highlight the importance of miR-874 in gastric cancer development and progression. 相似文献17.
Shoichiro Hikami Atsushi Shiozaki Maki Kitagawa-Juge Daisuke Ichikawa Toshiyuki Kosuga Hirotaka Konishi Shuhei Komatsu Hitoshi Fujiwara Kazuma Okamoto Eigo Otsuji 《Digestive diseases and sciences》2017,62(3):652-659
Background
The inhibitor of apoptosis protein (IAP) family are reported to play important roles in cancer cells evading apoptosis. However, the significance of their expression in human esophageal squamous cell carcinoma (ESCC) cells remains uncertain.Aims
The present study aimed to investigate the role of the IAP family members in tumor necrosis factor-α (TNF-α)-induced apoptosis of human ESCC cells.Methods
Five human ESCC cell lines were pretreated with TNF-α, cycloheximide (CHX, protein synthesis inhibitor), epoxomicin (proteasome inhibitor). Apoptosis assay and protein study with Western blot testing were conducted. Knockdown experiments with IAP siRNA were conducted, and the effect on cell apoptosis was analyzed.Results
Significant apoptosis was induced in five ESCC cell lines by TNF-α plus CHX stimulation, but not when treated with TNF-α or CHX alone. The protein expression levels of cIAP1 and XIAP were decreased by treatment with TNF-α in the presence of CHX, and the degree of cIAP1 and XIAP expression decrease was correlated with sensitivity to TNF-α plus CHX-induced apoptosis. Epoxomicin suppressed TNF-α plus CHX-induced degradation of survivin, cIAP1, and XIAP, in addition to apoptosis. A caspase inhibitor (z-VAD-fmk) suppressed TNF-α plus CHX-induced apoptosis, but did not suppress degradation of survivin, cIAP1, and XIAP. Furthermore, cIAP1 or XIAP siRNA transfected cells underwent apoptosis in response to treatment with TNF-α alone. Double knockdown of both genes resulted in further increased apoptosis.Conclusion
cIAP1 and XIAP play an essential role in the resistance of ESCC cells against apoptosis.18.
Xu L Wang F Liu H Xu XF Mo WH Xia YJ Wan R Wang XP Guo CY 《Digestive diseases and sciences》2011,56(6):1645-1655
Background
The cellular repressor of E1A-stimulated genes (CREG), a secreted glycoprotein, has been studied with human embryonic carcinoma cells, vascular smooth muscle cells, and NIH3T3 fibroblasts. However, its relationship to tumor cell proliferation and metastasis has not been examined in human gastric cancers (GC) until now.Aim
To investigate the expression of CREG in GC and its association with GC cell proliferation and metastasis.Methods
Forty-two cases of GCs, matched normal gastric tissues, and the human gastric cancer cell lines BGC-823, SGC-7901, MKN45, normal gastric mucosa cell line GES, and HUVEC cell line ECV304 were used to analyze CREG expression at the level of mRNA and protein. The expression of CREG was then further examined by immunohistochemistry in 42 GC tissues, and the correlation between the level of CREG and the pathological and clinical data was evaluated. Finally, we down-regulated the expression of CREG in GC cells with specific siRNA, and assessed the role of CREG in the proliferation and metastasis/invasion of the GC cell line.Results
The level of CREG was found to be higher in malignant GC tissues and cells compared to adjacent normal tissues and normal gastric cells (p < 0.001). Additionally, the expression levels of CREG were positively correlated with tumor clinical stage (p = 0.001), tumor metastasis (p < 0.001), and stages of tumor infiltration (p = 0.019). Furthermore, by using siRNA, we found that the down-regulated expression of CREG inhibited the proliferation of GC cells (p < 0.05), and migration of both GC cells (p = 0.001).Conclusions
Our data suggest that CREG plays an important role in gastric cancer cell proliferation and metastasis and that CREG may be a potential therapeutic target for GC. 相似文献19.
Shuhei Komatsu Daisuke Ichikawa Shoji Hirajima Hiroki Takeshita Atsushi Shiozaki Hitoshi Fujiwara Tsutomu Kawaguchi Mahito Miyamae Hirotaka Konishi Takeshi Kubota Kazuma Okamoto Nobuaki Yagi Eigo Otsuji 《Digestive diseases and sciences》2014,59(6):1152-1159
Background
This study was designed to evaluate the clinical benefit of predicting the cyclin D1 (CCND1) status using cell-free plasma DNA in superficial esophageal squamous cell carcinoma (ESCC) patients.Methods
The ratio of the CCND1 (11q13) dosage to the DRD2 (11q22–23) dosage (C/D ratio) as the CCND1 copy number was evaluated. This study was divided into three steps: (1) demonstration of the feasibility, (2) evaluation of whether the plasma C/D ratio assay could monitor tumor dynamics, and (3) a validation study in 63 consecutive superficial ESCC (pTis-T1) patients and 40 healthy volunteers.Results
(1) The plasma C/D ratio was significantly higher (p = 0.0369) in superficial ESCC patients than in the controls in a preliminary test. (2) The high plasma C/D ratio appeared to reflect the tumor levels of the CCND1 status and was reduced in postoperative plasma samples (p = 0.1154) and samples following endoscopic resection (p = 0.0845). (3) Validation analysis revealed that the plasma C/D ratio was significantly higher in superficial ESCC patients than in controls (p < 0.0001). The frequency of recurrence was significantly higher (p = 0.0198), and recurrence-free survival was significantly shorter (p = 0.0075) in patients with a high plasma C/D ratio. Moreover, a high C/D ratio was shown to be an independent risk factor for recurrence on multivariate analysis [p = 0.0334; odds ratio 10.58 (range 1.203–93.23)].Conclusion
The prediction of CCND1 amplification by plasma DNA may be a new complementary clinical biomarker for recurrence in patients with superficial ESCC. 相似文献20.
Na Wang Chao-qi Zhang Jia-huan He Xiao-fei Duan Yuan-yuan Wang Xiang Ji Wen-qiao Zang Min Li Yun-yun Ma Tao Wang Guo-qiang Zhao 《Digestive diseases and sciences》2013,58(7):1863-1870