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Sun J, Zhou F, Xue J, Ji C, Qu Y, Pan Y. Long non-coding RNA TRPM2-AS regulates microRNA miR-138-5p and PLAU (Plasminogen Activator, Urokinase) to promote the progression of gastric adenocarcinoma. Bioengineered 2021; 12:9753-9765. [PMID: 34696681 PMCID: PMC8809918 DOI: 10.1080/21655979.2021.1995101] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Gastric adenocarcinoma (GAC) is a common malignant tumor, accounting for 95% of gastric cancers. However, the effects and regulatory mechanisms of long non-coding RNA TRPM2-AS (TRPM2-AS) in GAC have not been fully explored. Our study investigates the action mechanism of TRPM2-AS in GAC. After performing quantitative Real-Time polymerase chain reaction or western blotting, we found that the levels of TRPM2-AS and Plasminogen Activator, Urokinase (PLAU) were upregulated in GAC, whereas the level of miR-138-5p was downregulated. Cell function experiments proved that silencing TRPM2-AS suppressed proliferation and migration and induced apoptosis in GAC cells. Bioinformatic analysis and luciferase assay identified the interaction between TRPM2-AS, miR-138-5p, and PLAU. In addition, the inhibitory effect of silencing TRPM2-AS on GAC cells could be partially relieved by PLAU overexpression. In conclusion, our study revealed that TRPM2-AS sponging miR-138-5p to upregulate PLAU could contribute to GAC progression, which might be useful for identifying biomarkers for GAC therapy.
Abbreviation
Gastric adenocarcinoma (GAC); Long non-coding RNA (lncRNA); lncRNA TRPM2 antisense RNA (TRPM2-AS); Plasminogen Activator, Urokinase (PLAU); Wild-type (WT); mutant (MUT).
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Affiliation(s)
- Jun Sun
- Department of Gastroenterology, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, Hubei, China
| | - Fang Zhou
- Department of Gastroenterology, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, Hubei, China
| | - Juan Xue
- Department of Gastroenterology, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, Hubei, China
| | - Chunyan Ji
- Department of Gastroenterology, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, Hubei, China
| | - Yinzong Qu
- Department of Gastroenterology, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, Hubei, China
| | - Yuwei Pan
- Department of Preventive Medicine, Tianhe District Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong, China
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Abdolahi S, Ghazvinian Z, Muhammadnejad S, Ahmadvand M, Aghdaei HA, Ebrahimi-Barough S, Ai J, Zali MR, Verdi J, Baghaei K. Adaptive NK Cell Therapy Modulated by Anti-PD-1 Antibody in Gastric Cancer Model. Front Pharmacol 2021; 12:733075. [PMID: 34588986 PMCID: PMC8473695 DOI: 10.3389/fphar.2021.733075] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 08/12/2021] [Indexed: 12/15/2022] Open
Abstract
Recently, adaptive NK cell therapy has become a promising treatment but has limited efficacy as a monotherapy. The identification of immune checkpoint inhibitor (ICI) molecules has opened a new horizon of immunotherapy. Herein, we aimed to demonstrate the cytotoxic effects of a polytherapy consisting of ex vivo expanded IL-2-activated NK cells combined with human anti-PD-1 antibody as an important checkpoint molecule in a xenograft gastric cancer mouse model. EBV-LCL cell is used as a feeder to promote NK cell proliferation with a purity of 93.4%. Mice (NOG, female, 6–8 weeks old) with xenograft gastric tumors were treated with PBS, ex vivo IL-2-activated NK cells, IL-2-activated NK cell along with human anti-PD-1 (Nivolumab), and IL-2-activated pretreated NK cells with anti-PD-1 antibody. The cytotoxicity of ex vivo expanded NK cells against MKN-45 cells was assessed by a lactate dehydrogenase (LDH) assay. Tumor volume was evaluated for morphometric properties, and tumor-infiltrating NK cells were assessed by immunohistochemistry (IHC) and quantified by flow cytometry. Pathologic responses were considered by H and E staining. Ex vivo LDH evaluation showed the cytotoxic potential of treated NK cells against gastric cancer cell line. We indicated that the adoptive transfer of ex vivo IL-2-activated NK cells combined with anti-PD-1 resulted in tumor growth inhibition in a xenograft gastric cancer model. Mitotic count was significantly decreased (*p < 0.05), and the tumor was associated with improved infiltration of NK cells in the NK-anti-PD-1 pretreated group (*p < 0.05). In conclusion, the combination approach of activated NK cells and anti-PD-1 therapy results in tumor growth inhibition, accompanied by tumor immune cell infiltration in the gastric tumor model.
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Affiliation(s)
- Shahrokh Abdolahi
- Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Zeinab Ghazvinian
- Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Samad Muhammadnejad
- Cell-Based Therapies Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Ahmadvand
- Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Science, Tehran, Iran.,Department of Hematology and Applied Cell Sciences, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Somayeh Ebrahimi-Barough
- Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Jafar Ai
- Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Javad Verdi
- Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Kaveh Baghaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Chen MH, Lu SN, Chen CH, Lin PC, Jiang JK, D’yachkova Y, Lukanowski M, Cheng R, Chen LT. How May Ramucirumab Help Improve Treatment Outcome for Patients with Gastrointestinal Cancers? Cancers (Basel) 2021; 13:3536. [PMID: 34298750 PMCID: PMC8306041 DOI: 10.3390/cancers13143536] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/24/2021] [Accepted: 07/09/2021] [Indexed: 12/24/2022] Open
Abstract
GI cancers are characterized by high recurrence rates and a dismal prognosis and there is an urgent need for new therapeutic approaches. This is a narrative review designed to provide a summary of the efficacy as measured by overall survival, progression free survival, and safety data from phase 3 randomized controlled GI clinical trials of ramucirumab including those from important pre-specified patient subgroups and evidence from real clinical practice worldwide. Quality of life (QOL) is discussed where data are available. Our aim was to summarize the efficacy and safety of ramucirumab in the treatment of GI cancers using these existing published data with a view to demonstrating how ramucirumab may help improve treatment outcome for patients with GI cancers. The data indicate that ramucirumab is efficacious, safe, and tolerable across the intent-to-treat patient populations as a whole and across several pre-specified subgroups, even those whose disease is traditionally more difficult to treat. Furthermore, survival outcomes observed in real-world clinical practice demonstrate similar data from phase 3 clinical trials even in patients with complications, suggesting that the benefits of ramucirumab translate in actual clinical practice.
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Affiliation(s)
- Ming-Huang Chen
- Taipei Veterans General Hospital, Taipei 11217, Taiwan; (M.-H.C.); (J.-K.J.)
| | - Sheng-Nan Lu
- Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City 83301, Taiwan;
| | - Chien-Hung Chen
- Department of Internal Medicine, National Taiwan University Hospital, Douliu 64041, Taiwan;
| | - Peng-Chan Lin
- National Cheng Kung University Hospital, National Cheng Kung University, Tainan 70403, Taiwan;
| | - Jeng-Kai Jiang
- Taipei Veterans General Hospital, Taipei 11217, Taiwan; (M.-H.C.); (J.-K.J.)
| | | | - Mariusz Lukanowski
- Global Medical Affairs, Eli Lilly Denmark, Hovedstaden, 2730 Herlev, Denmark;
| | - Rebecca Cheng
- Eli Lilly and Company (Taiwan) Inc., Taipe City 10543, Taiwan;
| | - Li-Tzong Chen
- National Cheng Kung University Hospital, National Cheng Kung University, Tainan 70403, Taiwan;
- National Institute of Cancer Research, National Health Research Institutes, Tainan 70456, Taiwan
- Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City 80756, Taiwan
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An CX, Xie SP, Li HL, Hu YH, Niu R, Zhang LJ, Jiang Y, Li Q, Zhou YN. Knockdown of Microtubule Associated Serine/threonine Kinase Like Expression Inhibits Gastric Cancer Cell Growth and Induces Apoptosis by Activation of ERK1/2 and Inactivation of NF-κB Signaling. Curr Med Sci 2021; 41:108-117. [PMID: 33582914 DOI: 10.1007/s11596-021-2325-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Accepted: 09/01/2020] [Indexed: 12/11/2022]
Abstract
Microtubule-associated serine/threonine kinase (MASTL) functions to regulate chromosome condensation and mitotic progression. Therefore, aberrant MASTL expression is commonly implicated in various human cancers. This study analyzed MASTL expression in gastric cancer vs. adjacent normal tissue for elucidating the association with clinicopathological data from patients. This work was then extended to investigate the effects of MASTL knockdown on tumor cells in vitro. The level of MASTL expression in gastric cancer tissue was assessed from the UALCAN, GEPIA, and Oncomine online databases. Lentivirus carrying MASTL or negative control shRNA was infected into gastric cancer cells. RT-qPCR, Western blotting, cell viability, cell counting, flow cytometric apoptosis and cell cycle, and colony formation assays were performed. MASTL was upregulated in gastric cancer tissue compared to the adjacent normal tissue, and the MASTL expression was associated with advanced tumor stage, Helicobacter pylori infection and histological subtypes. On the other hand, knockdown of MASTL expression significantly reduced tumor cell viability and proliferation, and arrested cell cycle at G2/M stage but promoted tumor cells to undergo apoptosis. At protein level, knockdown of MASTL expression enhanced levels of cleaved PARP1, cleaved caspase-3, Bax and p-ERK1/2 expression, but downregulated expression levels of BCL-2 and p-NF-κB-p65 protein in AGS and MGC-803 cells. MASTL overexpression in gastric cancer tissue may be associated with gastric cancer development and progression, whereas knockdown of MASTL expression reduces tumor cell proliferation and induces apoptosis. Further study will evaluate MASTL as a potential target of gastric cancer therapeutic strategy.
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Affiliation(s)
- Cai-Xia An
- Division of Gastroenterology and Hepatology, The First Hospital of Lanzhou University, Lanzhou, 730000, China
| | - Shou-Pin Xie
- Department of Neurology, The First People's Hospital of Lanzhou City, Lanzhou, 730050, China
| | - Hai-Long Li
- Department of Internal Mddicine, The First School of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou, 730000, China
| | - Yong-Hua Hu
- Department of Internal Mddicine, The First School of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou, 730000, China
| | - Rong Niu
- Department of External Chest, Gansu Provincial Cancer Hospital, Lanzhou, 730030, China
| | - Lin-Jie Zhang
- Division of Pediatric Emergency, Gansu Provincial Maternal and Child Health Hospital, Lanzhou, 730050, China
| | - Yan Jiang
- Division of Pediatric Emergency, Gansu Provincial Maternal and Child Health Hospital, Lanzhou, 730050, China
| | - Qiang Li
- Division of Neurosurgery, The Second Hospital of Lanzhou University, Lanzhou, 730000, China
| | - Yong-Ning Zhou
- Division of Gastroenterology and Hepatology, The First Hospital of Lanzhou University, Lanzhou, 730000, China.
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Sun H, Wu P, Zhang B, Wu X, Chen W. MCM3AP-AS1 promotes cisplatin resistance in gastric cancer cells via the miR-138/FOXC1 axis. Oncol Lett 2021; 21:211. [PMID: 33510812 PMCID: PMC7836396 DOI: 10.3892/ol.2021.12472] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 12/14/2020] [Indexed: 12/24/2022] Open
Abstract
The dysregulation of long non-coding RNAs (lncRNAs) serves a pivotal role in the pathogenesis and development of multiple types of human cancer, including gastric cancer (GC). MCM3AP-antisense 1 (MCM3AP-AS1) has been reported to function as a tumor promoter in various types of cancer. However, the biological function of MCM3AP-AS1 in the resistance of GC cells to cisplatin (CDDP) remains to be elucidated. The present study aimed to elucidate the mechanisms of MCM3AP-AS1 in the resistance of GC cells to CDDP. The expression levels of MCM3AP-AS1, miR-138 and FOXC1 were measured via reverse transcription-quantitative PCR. In addition, cell viability, migration and invasion were assessed via the Cell Counting Kit-8, wound healing and transwell assays, respectively. The interaction between genes was confirmed via the dual-luciferase reporter and pull-down assays. Western blot analysis was performed to detect FOXC1 protein expression. In the present study, it was demonstrated that MCM3AP-AS1 expression was upregulated in CDDP-resistant GC cells and that MCM3AP-AS1-knockdown suppressed CDDP resistance in GC cells. Moreover, the examination of the molecular mechanism indicated that MCM3AP-AS1 upregulated FOXC1 expression by sponging microRNA (miR)-138. Additionally, it was identified that the overexpression of FOXC1 abolished MCM3AP-AS1-knockdown- or miR-138 mimic-mediated inhibitory effects on CDDP resistance in GC cells. In conclusion, the present findings suggested that MCM3AP-AS1 enhanced CDDP resistance by sponging miR-138 to upregulate FOXC1 expression, indicating that MCM3AP-AS1 may be a novel promising biomarker for the diagnosis and treatment of patients with GC.
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Affiliation(s)
- Han Sun
- Department of Digestive Internal Medicine, Xuzhou Central Hospital, Xuzhou, Jiangsu 221000, P.R. China
| | - Ping Wu
- Department of Digestive Internal Medicine, Xuzhou Central Hospital, Xuzhou, Jiangsu 221000, P.R. China
| | - Bao Zhang
- Department of Digestive Internal Medicine, Xuzhou Central Hospital, Xuzhou, Jiangsu 221000, P.R. China
| | - Xia Wu
- Department of Digestive Internal Medicine, Xuzhou Central Hospital, Xuzhou, Jiangsu 221000, P.R. China
| | - Weixu Chen
- Department of Digestive Internal Medicine, Xuzhou Central Hospital, Xuzhou, Jiangsu 221000, P.R. China
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El Halabi M, Horanieh R, Tamim H, Mukherji D, Jdiaa S, Temraz S, Shamseddine A, Barada K. The impact of age on prognosis in patients with gastric cancer: experience in a tertiary care centre. J Gastrointest Oncol 2020; 11:1233-1241. [PMID: 33456996 PMCID: PMC7807276 DOI: 10.21037/jgo-20-139] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Accepted: 09/04/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Gastric cancer (GC) is a leading cause of cancer-related death in the world and most patients have advanced disease upon presentation. The effect of age on prognosis in GC is controversial. We aimed to determine the impact of age on survival in patients with GC. METHODS This was a retrospective study of the medical records of Lebanese patients diagnosed with GC at the American University of Beirut Medical Center (AUBMC) between 2005 and 2014. Patients were divided into young (<65 years) and older groups (≥65 years). A multivariate analysis was done to determine the independent predictors of survival. Kaplan-Meier method was used for analysis of long-term survival outcomes. RESULTS The sample consisted of 156 patients. The mean age was 62.15 (SD 13.54). Most patients presented with stage 4 disease (62.2%) and poorly differentiated histology (66.4%). The most common symptoms were abdominal pain and weight loss. On bivariate analysis, advanced stage (P=0.02) and higher grade (P=0.04) were associated with increased mortality. Patients <65 years of age were significantly more likely to have poorly differentiated tumours, while patients ≥65 years had more comorbidities (P=0.001). The 5-year DFS were 35% and 37% for patients <65 years of age and ≥65 years of age, respectively (P=0.15). CONCLUSIONS Higher grade and advanced stage are associated with worse survival in patients with GC, but age did not seem to have an impact. Screening high risk patients and early diagnosis are necessary to improve survival.
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Affiliation(s)
- Maan El Halabi
- Department of Internal Medicine, American University of Beirut Medical Centre, Beirut, Lebanon
- Division of Gastroenterology, American University of Beirut Medical Centre, Beirut, Lebanon
| | - Renee Horanieh
- Department of Internal Medicine, American University of Beirut Medical Centre, Beirut, Lebanon
| | - Hani Tamim
- Clinical Research Institute, American University of Beirut Medical Centre, Beirut, Lebanon
| | - Deborah Mukherji
- Department of Internal Medicine, American University of Beirut Medical Centre, Beirut, Lebanon
- Division of Hematology and Oncology, American University of Beirut Medical Centre, Beirut, Lebanon
| | - Sara Jdiaa
- Department of Internal Medicine, American University of Beirut Medical Centre, Beirut, Lebanon
| | - Sally Temraz
- Department of Internal Medicine, American University of Beirut Medical Centre, Beirut, Lebanon
- Division of Hematology and Oncology, American University of Beirut Medical Centre, Beirut, Lebanon
| | - Ali Shamseddine
- Department of Internal Medicine, American University of Beirut Medical Centre, Beirut, Lebanon
- Division of Hematology and Oncology, American University of Beirut Medical Centre, Beirut, Lebanon
| | - Kassem Barada
- Department of Internal Medicine, American University of Beirut Medical Centre, Beirut, Lebanon
- Division of Gastroenterology, American University of Beirut Medical Centre, Beirut, Lebanon
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Chen Y, Li B, Wang J, Liu J, Wang Z, Mao Y, Liu S, Liao X, Chen J. Identification and verification of the prognostic value of the glutathione S-transferase Mu genes in gastric cancer. Oncol Lett 2020; 20:100. [PMID: 32831919 PMCID: PMC7439103 DOI: 10.3892/ol.2020.11961] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Accepted: 06/23/2020] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is one of the most frequently diagnosed gastrointestinal cancer types in the world. Novel prognostic biomarkers are required to predict the progression of GC. Glutathione S-transferase Mu (GSTM) belongs to a family of phase II enzymes that have been implicated in a number of cancer types. However, the prognostic value of the GSTM genes has not been previously investigated in GC. The Cancer Genome Atlas (TCGA) was used to evaluate mRNA expression levels of GSTMs in GC tissue samples. Overall survival (OS) rates, hazard ratios (HRs) and 95% CIs were calculated using the Cox logistic regression model and Kaplan-Meier (KM) analysis was performed. In addition, the KM plotter online database was used to validate mRNA expression and the prognostic value of GSMT family members in patients with GC. To predict the function of GSTM genes in these patients, several bioinformatics tools, including the Database for Annotation, Visualization and Integrated Discovery, gene multiple association network integration algorithm, Search Tool for the Retrieval of Interacting Genes/Proteins, Gene Set Enrichment Analysis (GSEA), nomogram and genome-wide co-expression analysis were used. In the present study, high expression of GSTM5 was indicated to be strongly associated with lower OS in patients with GC, according to the TCGA and KM plotter online databases (HR=1.47, 95% CI: 1.06-2.04, P=0.021; and HR=1.69, 95% CI: 1.42-2.01, P=1.6×10-9, respectively). The results from the GSEA and genome-wide co-expression analysis indicated that GSTM5 expression associated with several biological process terms, including 'adhesion', 'angiogenesis', 'apoptotic process', 'cell growth', 'proliferation', 'migration', 'Hedgehog signaling', 'MAPK signaling' and the 'TGF-β signaling pathway'. In conclusion, the present results indicated that GSTM5 may serve as a biomarker for GC prognosis and may be a potential therapeutic target for GC.
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Affiliation(s)
- Yeyang Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Bopei Li
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Junfu Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Jinlu Liu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Zhen Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Yuantian Mao
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Siyu Liu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Xiwen Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Junqiang Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
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Hu G, Sun N, Jiang J, Chen X. Establishment of a 5-gene risk model related to regulatory T cells for predicting gastric cancer prognosis. Cancer Cell Int 2020; 20:433. [PMID: 32908454 PMCID: PMC7470613 DOI: 10.1186/s12935-020-01502-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2019] [Accepted: 08/18/2020] [Indexed: 12/14/2022] Open
Abstract
Background Gastric cancer (GC) is one of the high-risk cancers that lacks effective methods for prognosis prediction. Therefore, we searched for immune cells related to the prognosis of GC and studied the role of related genes in GC prognosis. Methods In this study, we collected the mRNA data of GC from The Cancer Genome Atlas (TCGA) database and studied the immune cells that were closely related to the prognosis of GC. Spearman correlation analysis was performed to show the association between immune cell-related genes and the differentially expressed genes (DEGs) of GC. Univariate and multivariate Cox regression analyses were conducted on the immune cell-related genes with a high correlation with GC. A prognostic risk score model was constructed and the most significant feature genes were identified. Kaplan–Meier method was then used to compare the overall survival (OS) of patients with high-risk and low-risk, and receiver operating characteristic (ROC) analysis was used to assess the accuracy of the risk model. In addition, GC patients were grouped according to the median expression of the features genes, and survival analysis was further carried out. Results It was noted that regulatory T cells (Tregs) were significantly correlated with the prognosis of GC, and 172 genes related to Tregs were found to be closely associated with GC. An optimal prognostic risk model was constructed, and a 5-gene (including LRFN4, ADAMTS12, MCEMP1, HP and MUC15) signature-based risk score was established. Survival analysis showed significant difference in OS between low-risk and high-risk samples. ROC analysis results indicated that the risk model had a high accuracy for the prognosis prediction of samples (AUC = 0.717). The results of survival analysis on each feature gene based on expression levels were consistent with the results of multivariate Cox analysis for predicting the risk rate of the 5 genes. Conclusion These results proved that the 5-gene signature-based risk score could be used to predict the survival of GC patients, and these 5 genes were closely related to Tregs. These findings are of great significance for studying the role of immune cells and related immune factors in regulating the prognosis of GC.
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Affiliation(s)
- Gang Hu
- Department of Gastrointestinal Surgery, Yiwu Central Hospital, 699# Jiangdong Road, Jiangdong Street, 322000 Jinhua, China
| | - Ningjie Sun
- Department of Gastrointestinal Surgery, Yiwu Central Hospital, 699# Jiangdong Road, Jiangdong Street, 322000 Jinhua, China
| | - Jiansong Jiang
- Department of Gastrointestinal Surgery, Yiwu Central Hospital, 699# Jiangdong Road, Jiangdong Street, 322000 Jinhua, China
| | - Xiansheng Chen
- Department of Gastrointestinal Surgery, Yiwu Central Hospital, 699# Jiangdong Road, Jiangdong Street, 322000 Jinhua, China
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9
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Hsueh SW, Liu KH, Hung CY, Tsai CY, Hsu JT, Tsang NM, Hsueh WH, Yang C, Chou WC. Predicting Postoperative Events in Patients With Gastric Cancer: A Comparison of Five Nutrition Assessment Tools. In Vivo 2020; 34:2803-2809. [PMID: 32871818 PMCID: PMC7652472 DOI: 10.21873/invivo.12106] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 05/15/2020] [Accepted: 05/16/2020] [Indexed: 01/14/2023]
Abstract
BACKGROUND/AIM We compared the adequacy of five nutrition assessment tools with respect to their predictive value in patients with locally advanced gastric cancer (GC) receiving radical surgery. PATIENTS AND METHODS Five nutrition assessment tools-Glasgow prognostic score (GPS), malnutritional universal screening tool (MUST), nutritional risk screening, patient generated subjective global assessment (PG-SGA), and prognostic nutritional index (PNI)-were assessed preoperatively for stage III GC patients. The correlation between postoperative events and nutritional status was further analyzed. RESULTS Most of the nutritional tools accurately predicted length of hospital stay and grade 3 or higher surgical complications, while only the GPS correlated with 30-day readmission and surgical complications. The PG-SGA performed the poorest among the five tools and failed to predict any postoperative event. CONCLUSION The application of GPS is recommended as a prognostic index for patients with locally advanced GC prior to radical surgery.
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Affiliation(s)
- Shun-Wen Hsueh
- Department of Oncology, Chang Gung Memorial Hospital at Keelung, Keelung, Taiwan, R.O.C
| | - Keng-Hao Liu
- Department of Surgery, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taoyuan, Taiwan, R.O.C
| | - Chia-Yen Hung
- Department of Hematology and Oncology, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taoyuan, Taiwan, R.O.C
- Division of Hema-oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan, R.O.C
| | - Chun-Yi Tsai
- Department of Surgery, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taoyuan, Taiwan, R.O.C
| | - Jun-Te Hsu
- Department of Surgery, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taoyuan, Taiwan, R.O.C
| | - Ngan-Ming Tsang
- Department of Radiation Oncology, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taoyuan, Taiwan, R.O.C
| | | | - Chieh Yang
- Department of Internal Medicine, En-Hua Hospital, New Taipei City, Taiwan, R.O.C
| | - Wen-Chi Chou
- Department of Hematology and Oncology, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taoyuan, Taiwan, R.O.C.
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Ma P, Li L, Liu F, Zhao Q. HNF1A-Induced lncRNA HCG18 Facilitates Gastric Cancer Progression by Upregulating DNAJB12 via miR-152-3p. Onco Targets Ther 2020; 13:7641-7652. [PMID: 32801777 PMCID: PMC7413704 DOI: 10.2147/ott.s253391] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 06/11/2020] [Indexed: 12/17/2022] Open
Abstract
Background The aberrant expression of long non-coding RNAs (lncRNAs) plays a pivotal role in the development and progression of multiple cancers, including gastric cancer (GC). However, the underlying molecular mechanisms of lncRNA HCG18 in GC remain unknown. Materials and Methods The expression levels of HCG18, HNF1A, microRNA-152-3p (miR-152-3p), and DNAJB12 were determined by RT-qPCR. Cell viability, migration, and invasion were assessed by CCK-8, wound healing, and transwell assays, respectively. The interaction between miR-152-3p and HCG18 or DNAJB12 was predicted by bioinformatics analysis and verified by dual-luciferase reporter assay. The correlation between the gene expression levels was analyzed using Pearson’s correlation coefficient. Western blot was used to measure the levels of HNF1A, DNAJB12, epithelial-mesenchymal transition (EMT) proteins (E-cadherin and Vimentin), and proliferation-related protein (PCNA). Results It was found that HCG18 was upregulated in GC tissues and cell lines, and knockdown of HCG18 inhibited the proliferation, migration, and invasion of GC cells. Patients with high HCG18 expression had a shorter overall survival time compared with those with low HCG18 expression. In addition, transcription factor HNF1A could bind to the HCG18 promoter to facilitate its transcription. The upregulation of HCG18 could abolish the inhibitory effect of miR-152-3p overexpression on GC cell progression. Furthermore, DNAJB12 was demonstrated to be a target gene of miR-152-3p in GC cells, and HCG18 enhanced DNAJB12 expression by competitively binding with miR-152-3p. Finally, rescue assays proved that overexpression of DNAJB12 partially restored HCG18 knockdown-attenuated progression of GC cells. Conclusion Our results demonstrated that HNF1A-induced HCG18 overexpression promoted GC progression by competitively binding with miR-152-3p and upregulating DNAJB12 expression. These findings might provide potential treatment strategies for patients with GC.
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Affiliation(s)
- Pei Ma
- Department of General Surgery, Nanyang First People's Hospital, Nanyang City, Henan Province, People's Republic of China
| | - Lianhai Li
- Department of General Surgery, Nanyang First People's Hospital, Nanyang City, Henan Province, People's Republic of China
| | - Fu Liu
- Department of General Surgery, Nanyang First People's Hospital, Nanyang City, Henan Province, People's Republic of China
| | - Qi Zhao
- Department of Urological Surgery, Nanyang First People's Hospital, Nanyang City, Henan Province, People's Republic of China
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11
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Ni P, Yu M, Zhang R, He M, Wang H, Chen S, Duan G. Prognostic Significance of ADAM17 for Gastric Cancer Survival: A Meta-Analysis. MEDICINA (KAUNAS, LITHUANIA) 2020; 56:322. [PMID: 32610677 PMCID: PMC7404708 DOI: 10.3390/medicina56070322] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 06/14/2020] [Accepted: 06/25/2020] [Indexed: 12/24/2022]
Abstract
Background and objectives: The prognostic role of a disintegrin and metalloproteinase (ADAM) 17 has been widely assessed in gastric cancer. However, the results are inconsistent. We performed a meta-analysis to evaluate the prognostic significance of ADAM17 and its association with clinicopathological parameters. Methods: The databases of PubMed, Web of Science, and Embase were searched for relevant articles published up to April 2020. The reported hazard ratios (HRs) and odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were pooled to evaluate the strength of the association. Stata 12.1 was used to perform statistical analyses. Results: Seven studies, including 1757 patients, were screened for the meta-analysis. Compared with the high ADAM17 expression group, the pooled HR was higher in the low ADAM17 expression group (HR = 2.04, 95% CI 1.66-2.50; I2 = 18.1%; p = 0.299). High ADAM17 expression was also related to the tumor node metastasis (TNM) stages (OR = 4.09, 95% CI 1.85-9.04; I2 = 84.1%; p = 0.000), lymph node metastasis (OR = 3.08, 95% CI 1.13-8.36; I2 = 79.7%; p = 0.007), and ages (OR = 1.65, 95% CI 1.24-2.21; I2 = 0%; p = 0.692) of the gastric patients. Conclusions: This meta-analysis revealed that ADAM17 is a significant biomarker for poor prognosis in gastric cancer.
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Affiliation(s)
- Peng Ni
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China; (P.N.); (M.Y.); (M.H.); (H.W.); (S.C.); (G.D.)
| | - Mingyang Yu
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China; (P.N.); (M.Y.); (M.H.); (H.W.); (S.C.); (G.D.)
| | - Rongguang Zhang
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China; (P.N.); (M.Y.); (M.H.); (H.W.); (S.C.); (G.D.)
- College of Public Health, Hainan Medical University, Haikou 571199, China
| | - Mengya He
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China; (P.N.); (M.Y.); (M.H.); (H.W.); (S.C.); (G.D.)
| | - Haiyan Wang
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China; (P.N.); (M.Y.); (M.H.); (H.W.); (S.C.); (G.D.)
| | - Shuaiyin Chen
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China; (P.N.); (M.Y.); (M.H.); (H.W.); (S.C.); (G.D.)
| | - Guangcai Duan
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China; (P.N.); (M.Y.); (M.H.); (H.W.); (S.C.); (G.D.)
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12
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Gu E, Song W, Liu A, Wang H. SCDb: an integrated database of stomach cancer. BMC Cancer 2020; 20:490. [PMID: 32487193 PMCID: PMC7265634 DOI: 10.1186/s12885-020-06869-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Accepted: 04/15/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Stomach cancer (SC) is a type of cancer, which is derived from the stomach mucous membrane. As there are non-specific symptoms or no noticeable symptoms observed at the early stage, newly diagnosed SC cases usually reach an advanced stage and are thus difficult to cure. Therefore, in this study, we aimed to develop an integrated database of SC. METHODS SC-related genes were identified through literature mining and by analyzing the publicly available microarray datasets. Using the RNA-seq, miRNA-seq and clinical data downloaded from The Cancer Genome Atlas (TCGA), the Kaplan-Meier (KM) survival curves for all the SC-related genes were generated and analyzed. The miRNAs (miRanda, miRTarget2, PicTar, PITA and TargetScan databases), SC-related miRNAs (HMDD and miR2Disease databases), single nucleotide polymorphisms (SNPs, dbSNP database), and SC-related SNPs (ClinVar database) were also retrieved from the indicated databases. Moreover, gene_disease (OMIM and GAD databases), copy number variation (CNV, DGV database), methylation (PubMeth database), drug (WebGestalt database), and transcription factor (TF, TRANSFAC database) analyses were performed for the differentially expressed genes (DEGs). RESULTS In total, 9990 SC-related genes (including 8347 up-regulated genes and 1643 down-regulated genes) were identified, among which, 65 genes were further confirmed as SC-related genes by performing enrichment analysis. Besides this, 457 miRNAs, 20 SC-related miRNAs, 1570 SNPs, 108 SC-related SNPs, 419 TFs, 44,605 CNVs, 3404 drug-associated genes, 63 genes with methylation, and KM survival curves of 20,264 genes were obtained. By integrating these datasets, an integrated database of stomach cancer, designated as SCDb, (available at http://www.stomachcancerdb.org/) was established. CONCLUSIONS As a comprehensive resource for human SC, SCDb database will be very useful for performing SC-related research in future, and will thus promote the understanding of the pathogenesis of SC.
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Affiliation(s)
- Erli Gu
- Department of Gastroenterology, Jing'An District Centre Hospital of Shanghai (Huashan Hospital Fudan University Jing'An Branch), Shanghai, 200040, People's Republic of China
| | - Wei Song
- Yuanzi (Shanghai) Information Technology Co., Ltd, No. 259 Xikang Road, Jing'An District, Shanghai, 200040, People's Republic of China
| | - Ajing Liu
- Yuanzi (Shanghai) Information Technology Co., Ltd, No. 259 Xikang Road, Jing'An District, Shanghai, 200040, People's Republic of China
| | - Hong Wang
- Department of Gastroenterology, Jing'An District Centre Hospital of Shanghai (Huashan Hospital Fudan University Jing'An Branch), Shanghai, 200040, People's Republic of China.
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Wu C, Hu Y, Ning Y, Zhao A, Zhang G, Yan L. Long Noncoding RNA Plasmacytoma Variant Translocation 1 Regulates Cisplatin Resistance via miR-3619-5p/TBL1XR1 Axis in Gastric Cancer. Cancer Biother Radiopharm 2020; 35:741-752. [PMID: 32407172 DOI: 10.1089/cbr.2019.3342] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Background: Chemoresistance greatly hinders the treatment of gastric cancer (GC). Long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) has been corroborated to be involved in chemoresistance in diverse cancers, including GC. The authors' aim was to investigate the underlying molecular mechanism of PVT1 in cisplatin (DPP) resistance in GC. Methods: Quantitative real-time polymerase chain reaction was conducted to detect the expression levels of PVT1, microRNA (miR)-3619-5p, and transducin beta like 1 x-linked receptor 1 (TBL1XR1) in DDP-resistant GC tissues and cells. 3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry assay were used to check cell viability, half inhibition concentration (IC50), and apoptosis, respectively. The abilities of cell migration and invasion were evaluated by transwell assay. The protein levels of drug resistance-related proteins permeability glycoprotein (P-gp), glutathione s-transferase pi (GST-π), multidrug resistance-associated protein, and TBL1XR1 in samples were measured by Western blot. A xenograft tumor model was established to investigate the biological function of PVT1 in vivo. The starBase site was utilized to predict binding sites between miR-3619-5p and PVT1 or TBL1XR1, and the dual-luciferase reporter assay was performed to verify the interaction. Results: The levels of PVT1 and TBL1XR1 were significantly upregulated in DPP-resistant GC tissues and cells, while miR-3619-5p was notably declined. Knockdown of PVT1 enhanced DPP sensitivity of DPP-resistant GC cells. Also, knockdown of PVT1 enhanced the sensitivity of DPP-resistant GC cells to DPP and inhibited tumor growth in vivo. Meanwhile, PVT1 silencing decreased the expression of drug-resistant proteins. Moreover, PVT1 interacted with miR-3619-5p, and TBL1XR1 was a target of miR-3619-5p. Further studies indicated that downregulation of miR-3619-5p transposed PVT1 silencing- or TBL1XR1 silencing-mediated effects on viability, apoptosis, migration, and invasion of DPP-resistant GC cells. Conclusions: PVT1 silencing attenuated the DPP resistance in GC by downregulating TBL1XR1 via sponging miR-3619-5p.
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Affiliation(s)
- Chao Wu
- Department of Oncology, Liaocheng Cancer Prevention and Treatment Hospital, Liaocheng, China
| | - Yu Hu
- Department of Oncology, Liaocheng Cancer Prevention and Treatment Hospital, Liaocheng, China
| | - Yongjie Ning
- Department of Pathology, Liaocheng Cancer Prevention and Treatment Hospital, Liaocheng, China
| | - Aili Zhao
- Department of Radiology, Liaocheng People's Hospital, Liaocheng, China
| | - Guangwei Zhang
- Department of Cardiology, Liaocheng People's Hospital, Liaocheng, China
| | - Lin Yan
- Department of Oncology, Liaocheng Cancer Prevention and Treatment Hospital, Liaocheng, China
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14
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Lu Z, Luo T, Pang T, Du Z, Yin X, Cui H, Fang G, Xue X. MALAT1 promotes gastric adenocarcinoma through the MALAT1/miR-181a-5p/AKT3 axis. Open Biol 2019; 9:190095. [PMID: 31480991 PMCID: PMC6769293 DOI: 10.1098/rsob.190095] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Accepted: 08/01/2019] [Indexed: 12/13/2022] Open
Abstract
Gastric adenocarcinoma, which originates from the gastric mucosal epithelium, has the highest incidence among various malignant tumours in China. As a crucial long non-coding RNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been suggested to play an important role in many tumours. Here, we aimed to investigate the role and underlying mechanism of MALAT1 in gastric adenocarcinoma. Quantitative reverse transcription polymerase chain reaction was applied to determine the expression levels of MALAT1 in serum and cell lines. A CCK-8 assay and a clonogenic survival assay were used to examine cell proliferation and apoptosis. The protein level of RAC-γ serine/threonine-specific protein kinase (AKT3) was determined by western blot. Our results showed that MALAT1 was highly expressed in the serum of patients with gastric adenocarcinoma and in cell lines. Downregulating MALAT1 inhibited proliferation and promoted apoptosis of MGC-803 cells. In addition, MALAT1 directly targeted and decreased the expression of miR-181a-5p, which in turn upregulated the expression of AKT3. Further, overexpressing miR-181a-5p or directly inhibiting the AKT pathway with the inhibitor ipatasertib exhibited similar effects to MALAT1 knockdown. Our research proposes a novel mechanism where the role of MALAT1 is dependent on the MALAT1/miR-181a-5p/AKT3 axis. MALAT1 competes with AKT3 for miR-181a-5p binding, thereby upregulating the AKT3 protein level and ultimately promoting the growth of gastric adenocarcinoma.
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Affiliation(s)
- Zhengmao Lu
- Department of General Surgery, Changhai Hospital, the Second Military Medical University, SMMU, No. 168 Changhai Road, Yangpu District, Shanghai 200433, People's Republic of China
| | - Tianhang Luo
- Department of General Surgery, Changhai Hospital, the Second Military Medical University, SMMU, No. 168 Changhai Road, Yangpu District, Shanghai 200433, People's Republic of China
| | - Tao Pang
- Department of General Surgery, Changhai Hospital, the Second Military Medical University, SMMU, No. 168 Changhai Road, Yangpu District, Shanghai 200433, People's Republic of China
| | - Zongxin Du
- The People's Hospital of Gongliu, No. 71 East Ring Road, Gongliu County, Yili 835400, Xingjiang, People's Republic of China
| | - Xiaoyi Yin
- Department of General Surgery, Changhai Hospital, the Second Military Medical University, SMMU, No. 168 Changhai Road, Yangpu District, Shanghai 200433, People's Republic of China
| | - Hangtian Cui
- Department of General Surgery, Changhai Hospital, the Second Military Medical University, SMMU, No. 168 Changhai Road, Yangpu District, Shanghai 200433, People's Republic of China
| | - Guoen Fang
- Department of General Surgery, Changhai Hospital, the Second Military Medical University, SMMU, No. 168 Changhai Road, Yangpu District, Shanghai 200433, People's Republic of China
| | - Xuchao Xue
- Department of General Surgery, Changhai Hospital, the Second Military Medical University, SMMU, No. 168 Changhai Road, Yangpu District, Shanghai 200433, People's Republic of China
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15
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Li W, Chen Y, Sun X, Yang J, Zhang DY, Wang D, Suo J. Protein expression profiles and clinicopathologic characteristics associate with gastric cancer survival. Biol Res 2019; 52:42. [PMID: 31399040 PMCID: PMC6689162 DOI: 10.1186/s40659-019-0249-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Accepted: 08/01/2019] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Prognosis remains one of most crucial determinants of gastric cancer (GC) treatment, but current methods do not predict prognosis accurately. Identification of additional biomarkers is urgently required to identify patients at risk of poor prognoses. METHODS Tissue microarrays were used to measure expression of nine GC-associated proteins in GC tissue and normal gastric tissue samples. Hierarchical cluster analysis of microarray data and feature selection for factors associated with survival were performed. Based on these data, prognostic scoring models were established to predict clinical outcomes. Finally, ingenuity pathway analysis (IPA) was used to identify a biological GC network. RESULTS Eight proteins were upregulated in GC tissues versus normal gastric tissues. Hierarchical cluster analysis and feature selection showed that overall survival was worse in cyclin dependent kinase (CDK)2, Akt1, X-linked inhibitor of apoptosis protein (XIAP), Notch4, and phosphorylated (p)-protein kinase C (PKC) α/β2 immunopositive patients than in patients that were immunonegative for these proteins. Risk score models based on these five proteins and clinicopathological characteristics were established to determine prognoses of GC patients. These proteins were found to be involved in cancer related-signaling pathways and upstream regulators were identified. CONCLUSION This study identified proteins that can be used as clinical biomarkers and established a risk score model based on these proteins and clinicopathological characteristics to assess GC prognosis.
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Affiliation(s)
- Wei Li
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, 130021, Jilin, China.,Jilin Province Key Laboratory of Bioinformatics for Gastrointestinal Tumor, Changchun, Jilin, China
| | - Yan Chen
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, 130021, Jilin, China
| | - Xuan Sun
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, 130021, Jilin, China
| | - Jupeng Yang
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, 130021, Jilin, China
| | - David Y Zhang
- Department of Pathology, Mount Sinai School of Medicine, New York, NY, USA
| | - Daguang Wang
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, 130021, Jilin, China.
| | - Jian Suo
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, 130021, Jilin, China. .,Jilin Province Key Laboratory of Bioinformatics for Gastrointestinal Tumor, Changchun, Jilin, China.
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16
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Li H, He C, Wang X, Wang H, Nan G, Fang L. MicroRNA-183 affects the development of gastric cancer by regulating autophagy via MALAT1-miR-183-SIRT1 axis and PI3K/AKT/mTOR signals. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2019; 47:3163-3171. [PMID: 31352788 DOI: 10.1080/21691401.2019.1642903] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- Huiying Li
- China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Chengyan He
- China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Xuekui Wang
- China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Hai Wang
- China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Guangxian Nan
- China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Ling Fang
- China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
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17
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Nie ML, Han J, Huang HC, Guo T, Huangfu LT, Cheng XJ, Li XM, Du H, Li QD, Wen XZ, Ji JF. The novel lncRNA p4516 acts as a prognostic biomarker promoting gastric cancer cell proliferation and metastasis. Cancer Manag Res 2019; 11:5375-5391. [PMID: 31354346 PMCID: PMC6578592 DOI: 10.2147/cmar.s201793] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Accepted: 04/05/2019] [Indexed: 12/18/2022] Open
Abstract
Purpose: Emerging evidence has shown that long noncoding RNAs (lncRNAs) participate in oncogenesis and tumor progression. We previously found a novel lncRNA p4516 which was closely associated with prognosis by preliminary study of lncRNA expression profile from paired tumors and nontumor tissues in 198 gastric cancer (GC) patients. However, the exact biological functions and the underlying molecular mechanisms of p4516 in gastric tumorigenesis still remain unclear. Materials and methods: The RNA fluorescence in situ hybridization (RNA-FISH) analysis, cytoplasmic and nuclear RNA isolation and qRT-PCR were applied to determine the subcellular localization of p4516. Expression levels of p4516 were assessed using qRT-PCR in both GC cell lines and in 142 primary GC tissues. Correlations between p4516 expression and GC patients’ clinicopathological parameters were analyzed. Gain- and loss-of-function experiments were employed to investigate the role of p4516 in proliferation, migration and invasion both in vitro and in vivo. In addition, Western blotting and immunohistochemical staining were used to examine the protein expression levels. Results: LncRNA p4516 was mainly localized in the nucleus of GC cells and p4516 tended to have higher expression levels in GC cells compared to the normal gastric mucosa-derived cells GES-1. Furthermore, higher expression levels of p4516 correlated with worse clinical outcomes in GC patients and acted as an independent prognostic biomarker. Functional analysis revealed that p4516 participated in the regulation of GC cell proliferation, invasion and migration both in vivo and in vitro. Moreover, p4516 was involved in epithelial–mesenchymal transition (EMT) in GC cells. Conclusion: Our study demonstrated the oncogenic role of novel lncRNA p4516 in the gastric carcinogenesis for the first time. High expression of p4516 may act as prognostic marker in patient with gastric cancer.
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Affiliation(s)
- Meng-Lin Nie
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Jing Han
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Han-Chen Huang
- Key Laboratory of RNA Biology, Beijing Key Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.,Centre for Cognitive Machines and Computational Health (CMaCH), The School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, People's Republic of China
| | - Ting Guo
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Long-Tao Huangfu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Xiao-Jing Cheng
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Xiao-Mei Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Hong Du
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Qing-Da Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Xian-Zi Wen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Jia-Fu Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.,Department of Gastrointestinal Surgery, Peking University Cancer Hospital, Beijing, People's Republic of China
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18
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Wang X, Gao S, Xie F, Li W, Li M, Yan N, Gao T, Fang L. Retracted
: High expression of TCF12 contributes to gastric cancer development via being target regulated by miR‐183 and activating PI3K/AKT pathway. J Cell Biochem 2019; 120:13903-13911. [DOI: 10.1002/jcb.28664] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2018] [Revised: 01/23/2019] [Accepted: 01/24/2019] [Indexed: 02/06/2023]
Affiliation(s)
- Xuekui Wang
- Department of Breast and Thyroid Surgery China‐Japan Union Hospital of Jilin University Changchun Jilin China
| | - Shen Gao
- Department of Breast and Thyroid Surgery China‐Japan Union Hospital of Jilin University Changchun Jilin China
| | - Feng Xie
- Department of Breast and Thyroid Surgery China‐Japan Union Hospital of Jilin University Changchun Jilin China
| | - Wei Li
- Department of Breast and Thyroid Surgery China‐Japan Union Hospital of Jilin University Changchun Jilin China
| | - Miyang Li
- Department of Breast and Thyroid Surgery China‐Japan Union Hospital of Jilin University Changchun Jilin China
| | - Ning Yan
- Department of Breast and Thyroid Surgery China‐Japan Union Hospital of Jilin University Changchun Jilin China
| | - Tiehe Gao
- Department of Breast and Thyroid Surgery China‐Japan Union Hospital of Jilin University Changchun Jilin China
| | - Ling Fang
- Department of Breast and Thyroid Surgery China‐Japan Union Hospital of Jilin University Changchun Jilin China
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Liu R, Zhong J, Yu X, Li Y, Chen P. Identifying Critical State of Complex Diseases by Single-Sample-Based Hidden Markov Model. Front Genet 2019; 10:285. [PMID: 31019526 PMCID: PMC6458292 DOI: 10.3389/fgene.2019.00285] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Accepted: 03/15/2019] [Indexed: 12/20/2022] Open
Abstract
The progression of complex diseases is generally divided as a normal state, a pre-disease state or tipping point, and a disease state. Developing individual-specific method that can identify the pre-disease state just before a catastrophic deterioration, is critical for patients with complex diseases. However, with only a case sample, it is challenging to detect a pre-disease state which has little significant differences comparing with a normal state in terms of phenotypes and gene expressions. In this study, by regarding the tipping point as the end point of a stationary Markov process, we proposed a single-sample-based hidden Markov model (HMM) approach to explore the dynamical differences between a normal and a pre-disease states, and thus can signal the upcoming critical transition immediately after a pre-disease state. Using this method, we identified the pre-disease state or tipping point in a numerical simulation and two real datasets including stomach adenocarcinoma and influenza infection, which demonstrate the effectiveness of the method.
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Affiliation(s)
- Rui Liu
- School of Mathematics, South China University of Technology, Guangzhou, China
| | - Jiayuan Zhong
- School of Mathematics, South China University of Technology, Guangzhou, China
| | - Xiangtian Yu
- Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Yongjun Li
- School of Computer Science and Engineering, South China University of Technology, Guangzhou, China
| | - Pei Chen
- School of Mathematics, South China University of Technology, Guangzhou, China
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20
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Zhang F, Ma C. Kaempferol suppresses human gastric cancer SNU-216 cell proliferation, promotes cell autophagy, but has no influence on cell apoptosis. ACTA ACUST UNITED AC 2019; 52:e7843. [PMID: 30785478 PMCID: PMC6376319 DOI: 10.1590/1414-431x20187843] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2018] [Accepted: 11/19/2018] [Indexed: 02/06/2023]
Abstract
Gastric cancer remains a serious threat to human health worldwide. Kaempferol is a plant-derived flavonoid compound with a wide range of pharmacological activities. This study aimed to investigate the effects of kaempferol on gastric cancer SNU-216 cell proliferation, apoptosis, and autophagy, as well as underlying potential mechanisms. Viability, proliferation, and apoptosis of SNU-216 cells after kaempferol treatment were evaluated using cell counting kit-8 assay, 5-btomo-2′-deoxyuridine incorporation assay, and annexin V-FITC/PI staining, respectively. Quantitative reverse transcription PCR was performed to measure the mRNA expressions of cyclin D1 and microRNA-181a (miR-181a) in SNU-216 cells. Cell transfection was used to down-regulate the expression of miR-181a. The protein expression levels of cyclin D1, bcl-2, bax, caspase 3, caspase 9, autophagy-related gene 7, microtubule-associated protein 1 light chain 3-I (LC3-I), LC3-II, Beclin 1, p62, mitogen-activated protein kinase (MAPK), extracellular regulated protein kinases (ERK), and phosphatidylinositol 3 kinase (PI3K) in SNU-216 cells were detected using western blotting. Results showed that kaempferol significantly suppressed SNU-216 cell viability and proliferation but had no influence on cell apoptosis. Further results suggested that kaempferol significantly induced SNU-216 cell autophagy. The expression of miR-181a in SNU-216 cells after kaempferol treatment was enhanced. Kaempferol significantly inactivated MAPK/ERK and PI3K pathways in SNU-216 cells. Suppression of miR-181a significantly reversed the kaempferol-induced MAPK/ERK and PI3K pathways inactivation in SNU-216 cells. This research demonstrated that kaempferol suppressed proliferation and promoted autophagy of human gastric cancer SNU-216 cells by up-regulating miR-181a and inactivating MAPK/ERK and PI3K pathways.
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Affiliation(s)
- Fan Zhang
- Teaching and Research Department of Diagnostics, Jining Medical University, Jining, China
| | - Cuimei Ma
- Department of Gastroenterology, Affiliated Hospital of Jining Medical University, Jining, China
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21
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Li W, Wang D, Sun X, Zhang Y, Wang L, Suo J. ADAM17 promotes lymph node metastasis in gastric cancer via activation of the Notch and Wnt signaling pathways. Int J Mol Med 2018; 43:914-926. [PMID: 30569104 PMCID: PMC6317666 DOI: 10.3892/ijmm.2018.4028] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Accepted: 11/26/2018] [Indexed: 12/24/2022] Open
Abstract
Disintegrin and metalloproteinase domain-containing proteins (ADAMs) have been implicated in cell adhesion, signaling and migration. The aim of the present study was to identify key members of the ADAM protein family associated with the metastasis of gastric cancer and to evaluate their clinical significance. A total of 193 patients with gastric cancer and positive lymph node metastasis were enrolled. Key members of the ADAM family associated with lymph node metastasis were identified. The correlations between survival times and the clinicopathological features of patients were investigated. Furthermore, ADAM17 expression in gastric cancer cells with different metastatic potentials was determined. ADAM17 was overexpressed in BGC-823 cells and suppressed in SGC-7901 cells to further investigate its effects on cell viability and migration. The key pathways associated with ADAM17 were identified by gene set enrichment analysis (GSEA). It was found that ADAM9 and ADAM17 were significantly upregulated in gastric cancer and positive metastatic lymph node tissues. Further, there was a strong correlation between the survival times of patients and ADAM17 expression. ADAM17 was upregulated in gastric cancer cells with high metastatic potential. The viability of BGC-823 cells significantly increased following ADAM17 overexpression, whereas the viability and migration of SGC-7901 cells decreased following ADAM17 suppression. GSEA and western blot analysis revealed a positive correlation between the Notch and Wnt signaling pathways with ADAM17 expression. In conclusion, the increased expression of ADAM17 promoted the progression of gastric cancer, potentially via Notch and/or Wnt signaling pathway activation, and ADAM17 may serve as a useful prognostic marker.
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Affiliation(s)
- Wei Li
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Daguang Wang
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Xuan Sun
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Yang Zhang
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Lei Wang
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Jian Suo
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
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22
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Li L, Feng R, Fei S, Cao J, Zhu Q, Ji G, Zhou J. NANOGP8 expression regulates gastric cancer cell progression by transactivating DBC1 in gastric cancer MKN-45 cells. Oncol Lett 2018; 17:555-563. [PMID: 30655801 DOI: 10.3892/ol.2018.9595] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2017] [Accepted: 07/23/2018] [Indexed: 02/06/2023] Open
Abstract
NANOGP8 is one of the NANOG pseudogenes and is expressed together with NANOG in multiple tumor tissues and cell lines. The biological functions of NANOGP8 in progression of gastric cancer are unclear. In the present study, the role of NANOGP8 was investigated in gastric cancer cells. The gathered data demonstrated that NANOG expression in both mRNA and protein was elevated in gastric cancer cell lines relative to a normal gastric epithelial cell line. Downregulation of NANOGP8 inhibited cell proliferation and increased apoptosis in human gastric carcinoma cell lines. Furthermore, silencing of NANOGP8 suppressed tumor growth in vivo. Interestingly, it was identified that deleted in breast cancer 1 (DBC1) expression was also markedly downregulated following NANOGP8 knockdown. DNA microarray and dual-luciferase assays further indicated that NANOGP8 may bind to the DBC1 promoter region and regulate DBC1 expression. Therefore, the gathered data provided evidence that NANOGP8 contributes to progression of gastric cancer via DBC1 and may have potential translational significance.
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Affiliation(s)
- Li Li
- Department of Molecular Cell Biology and Toxicology, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.,Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221000, P.R. China
| | - Ru Feng
- Department of Geriatrics, Suqian People's Hospital Drum Tower Hospital Group, Suqian, Jiangsu 223800, P.R. China
| | - Sujuan Fei
- Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221000, P.R. China
| | - Jiang Cao
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221000, P.R. China
| | - Qinqin Zhu
- Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221000, P.R. China
| | - Guozhong Ji
- Department of Medical Examination Center and Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China
| | - Jianwei Zhou
- Department of Molecular Cell Biology and Toxicology, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China
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23
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Zhang W, Liu S, Zhan H, Yan Z, Zhang G. Transcriptome sequencing identifies key pathways and genes involved in gastric adenocarcinoma. Mol Med Rep 2018; 18:3673-3682. [PMID: 30106143 PMCID: PMC6131596 DOI: 10.3892/mmr.2018.9370] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Accepted: 07/03/2018] [Indexed: 12/19/2022] Open
Abstract
The present study aimed to investigate the key pathways and genes associated with gastric adenocarcinoma via transcriptome sequencing. Five pairs of gastric adenocarcinoma tissue and normal tumor-adjacent tissue were harvested. After sequencing, raw data were processed and differentially expressed genes (DEGs) between tumor and control groups were screened, followed by functional enrichment analysis and gene clustering analysis. The effect of DEGs on patient prognosis was analyzed on the basis of the survival data from gastric adenocarcinoma patients in The Cancer Genome Atlas database. Several genes were validated through reverse transcription-quantitative polymerase chain reaction. In total, 1,477 upregulated and 282 downregulated DEGs were screened in tumor groups. These genes were segregated into four clusters. Genes in cluster 1 were significantly involved in metabolism of xenobiotics by cytochrome P450, genes in cluster 2 were majorly involved in apoptosis, tight junction formation, and platelet activation, genes in cluster 3 were primarily enriched in the p53 signaling pathway and genes in cluster 4 were significantly enriched in the insulin resistance pathway. Furthermore, 15 DEGs significantly influenced prognosis, including F2R, CTHRC1, and RASGRP3. The expression levels of CYP2B6, MAPK13, CTHRC, RASGRP3 and PYGM were consistent with our analysis results. In conclusion, pathways for metabolism of xenobiotics via cytochrome P450, apoptosis, tight junction formation, platelet activation, and insulin resistance may serve important roles in the progression of gastric adenocarcinoma. Notably, CTHRC1 and RASGRP3 may serve as key prognostic markers.
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Affiliation(s)
- Wenhu Zhang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Shaozhuang Liu
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Hanxiang Zhan
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Zhibo Yan
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Guangyong Zhang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
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24
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Cao B, Liu C, Yang G. Down-regulation of lncRNA ADAMTS9-AS2 contributes to gastric cancer development via activation of PI3K/Akt pathway. Biomed Pharmacother 2018; 107:185-193. [PMID: 30089248 DOI: 10.1016/j.biopha.2018.06.146] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Revised: 06/21/2018] [Accepted: 06/27/2018] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVE We aimed to investigate the role and regulatory mechanism of lncRNA ADAMTS9-AS2 in the development of gastric cancer. MATERIALS AND METHODS The expression of lncRNA ADAMTS9-AS2 in gastric cancer tissues and cells was detected. According to the expression level of ADAMTS9-AS2, survival analysis for patients with gastric cancer was performed. In addition, SGC-7901 cells were transfected with pc-ADAMTS9-AS2, si-ADAMTS9-AS2 and scramble RNA (control) to investigate the effects of ADAMTS9-AS2 on cell proliferation, migration, invasion and apoptosis. Besides, the expression levels of key molecules involved in PI3K/Akt pathway were detected. RESULTS Results showed that lncRNA ADAMTS9-AS2 was significantly down-regulated in gastric cancer tissues and cells. Decreased expression of lncRNA ADAMTS9-AS2 was associated with poor prognosis in patients with gastric cancer. In comparison with control group, the SGC-7901 cell viability and the number of colony, migrated or invaded SGC-7901 cells of pc-ADAMTS9-AS2 group were significantly decreased while markedly increased in si-ADAMTS9-AS2 group. The percentage of apoptotic SGC-7901 cells in pc-ADAMTS9-AS2 group was significantly increased, while significantly decreased in si-ADAMTS9-AS2 group. Additionally, the expressions of p-PI3K and p-Akt were significantly down-regulated in pc-ADAMTS9-AS2 group compared with control group, while up-regulated in si-ADAMTS9-AS2 group. Furthermore, compared with si-ADAMTS9-AS2 group, treatment of an PI3K inhibitor LY294002 markedly reversed the effects of suppression of ADAMTS9-AS2 alone on SGC-7901 cells by inhibiting cell viability, colony-forming ability, migration, invasion, and increasing apoptosis. CONCLUSIONS Our results indicate that overexpression of ADAMTS9-AS2 may inhibit gastric cancer cell proliferation, suppress cancer cell migration and invasion, and induce cell apoptosis. Activation of PI3K/Akt pathway may be a key regulatory mechanism of ADAMTS9-AS2 in gastric cancer.
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Affiliation(s)
- Bole Cao
- Department of Gastroenterology, Taizhou People's hospital, Taizhou, Jiangsu 225300, China.
| | - Cuixia Liu
- Department of Gastroenterology, Taizhou People's hospital, Taizhou, Jiangsu 225300, China
| | - Guifeng Yang
- Department of Gastroenterology, Taizhou People's hospital, Taizhou, Jiangsu 225300, China
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25
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Inhibitor of growth 3 induces cell death by regulating cell proliferation, apoptosis and cell cycle arrest by blocking the PI3K/AKT pathway. Cancer Gene Ther 2018; 25:240-247. [DOI: 10.1038/s41417-018-0023-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2017] [Revised: 03/18/2018] [Accepted: 03/24/2018] [Indexed: 12/14/2022]
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26
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Liu Z, Yan Y, Cao S, Chen Y. Long non-coding RNA SNHG14 contributes to gastric cancer development through targeting miR-145/SOX9 axis. J Cell Biochem 2018; 119:6905-6913. [PMID: 29667771 DOI: 10.1002/jcb.26889] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2017] [Accepted: 03/21/2018] [Indexed: 12/11/2022]
Abstract
This study aimed to elucidate the roles of long non-coding RNA SNHG14 in gastric cancer development. LncRNA SNHG14 was markedly up-regulated in gastric cancer tissues and cells. Knockdown of SNHG14 significantly inhibited SGC-7901 cell viability, migration, invasion, and promoted cell apoptosis. In addition, miR-145 was negatively regulated by SNHG14 and the effects of SNHG14 knockdown on cell viability, apoptosis, migration, invasion, and the expression of apoptosis-related proteins and EMT-markers were reversed by inhibition of miR-145 at the same time. Furthermore, SOX9 was verified as a functional target of miR-145, and miR-145 regulated tumor malignant behaviors through regulating SOX9. Besides, knockdown of SNHG14 inhibited the expression of p-PI3 K, p-AKT, and p-mTOR and promoted PTEN expression, where miR-145 inhibition had opposite effects. Moreover, the activated PI3 K/AKT/mTOR pathway caused by miR-145 inhibition was counteracted after knockdown of SOX9. Our findings indicate that up-regulation of lncRNA SNHG14 may contribute to gastric cancer development via targeting miR-145/SOX9 axis and involving in PI3 K/AKT/mTOR pathway. SNHG14-miR-145/SOX9 axis may be a promising therapeutic strategy for gastric cancer treatment.
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Affiliation(s)
- Zhao Liu
- Department of Surgery, Xi'an Chest Hospital, Xi'an TB&Thoracic Tumor Hospital, Xi'an, Shanxi, China
| | - Yan Yan
- Institute of Cancer Research, School of Basic Medical Science of Xi'an Jiao Tong University, Xi'an, Shaanxi, China.,Department of Pathology, The First Hospital of Xi'an, Xi'an, Shaanxi, China
| | - Sizhe Cao
- Department of Medicine, Xi'an Chest Hospital, Xi'an TB&Thoracic Tumor Hospital, Xi'an, Shanxi, China
| | - Yi Chen
- Department of General Surgery, The Changan District Hospital of the First Affiliated Hospital, Xi'an Jiaotong University, Shanxi, China
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27
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Peng Y, Shen X, Jiang H, Chen Z, Wu J, Zhu Y, Zhou Y, Li J. miR-188-5p Suppresses Gastric Cancer Cell Proliferation and Invasion via Targeting ZFP91. Oncol Res 2018; 27:65-71. [PMID: 29471891 PMCID: PMC7848256 DOI: 10.3727/096504018x15191223015016] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
MicroRNAs (miRNAs) have been demonstrated to be essential regulators in the development and progression of various cancers. The role of miR-188-5p in gastric cancer (GC) has not been determined. In this study, we found that the expression of miR-188-5p was downregulated in GC tissues compared with adjacent normal tissues. The lowly expressed miR-188-5p was significantly associated with lymph node metastasis and advanced TNM stage. Moreover, overexpression of miR-188-5p significantly inhibited GC cell proliferation, migration, and invasion but promoted cellular apoptosis. Mechanistically, we identified transcription factor ZFP91 as a target gene of miR-188-5p in GC. We found that miR-188-5p overexpression significantly inhibited the expression of ZFP91 in GC cell lines. There was an inverse correlation between the expression of miR-188-5p and ZFP91 in GC tissues. We found that restoration of ZFP91 in miR-188-5p-overexpressed MGC-803 and SGC-7901 cells promoted cell proliferation, migration, and invasion. Finally, we also showed that overexpression of miR-188-5p inhibited tumor growth in vivo. Taken together, our findings indicated that miR-188-5p serves as a tumor suppressor in human GC by targeting ZFP91, suggesting that miR-188-5p might be a promising therapeutic target for GC treatment.
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Affiliation(s)
- Yuping Peng
- Department of Gastrointestinal Surgery, Jiaxing First Hospital, Jiaxing, Zhejiang Province, P.R. China
| | - Xuning Shen
- Department of Gastrointestinal Surgery, Jiaxing First Hospital, Jiaxing, Zhejiang Province, P.R. China
| | - Honggang Jiang
- Department of Gastrointestinal Surgery, Jiaxing First Hospital, Jiaxing, Zhejiang Province, P.R. China
| | - Zhiheng Chen
- Department of Gastrointestinal Surgery, Jiaxing First Hospital, Jiaxing, Zhejiang Province, P.R. China
| | - Jiaming Wu
- Department of Gastrointestinal Surgery, Jiaxing First Hospital, Jiaxing, Zhejiang Province, P.R. China
| | - Yi Zhu
- Department of Gastrointestinal Surgery, Jiaxing First Hospital, Jiaxing, Zhejiang Province, P.R. China
| | - Yuan Zhou
- Department of Gastrointestinal Surgery, Jiaxing First Hospital, Jiaxing, Zhejiang Province, P.R. China
| | - Jin Li
- Department of Gastrointestinal Surgery, Jiaxing First Hospital, Jiaxing, Zhejiang Province, P.R. China
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28
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Wang F, Zhang D, Mao J, Ke XX, Zhang R, Yin C, Gao N, Cui H. Morusin inhibits cell proliferation and tumor growth by down-regulating c-Myc in human gastric cancer. Oncotarget 2017; 8:57187-57200. [PMID: 28915664 PMCID: PMC5593635 DOI: 10.18632/oncotarget.19231] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Accepted: 06/26/2017] [Indexed: 02/07/2023] Open
Abstract
Morusin is a pure extract from the root bark of Morus australis (Moraceae). In recent years, morusin has been reported to exhibit anti-tumor biological activity in some types of human cancers through different mechanisms. Here, we attempted to investigate the inhibitory effect and mechanism of morusin on gastric cancer. Morusin markedly inhibited gastric cancer cell proliferation by down-regulating CDKs and Cyclins, such as CDK2, CDK4, Cyclin D1 and Cyclin E1. Additionally, morusin suppressed tumor growth in vitro and in vivo. Up-regulation of CDKs and Cyclins in gastric cancer cells was induced by c-Myc binding at the E-Box regions of CDKs and the Cyclin promoter. In addition, compared with the control group, the morusin-treated group showed reduced expression of c-Myc and c-Myc protein binding at the E-Box regions. Based on these results, we overexpressed c-Myc in gastric cancer cells and found that overexpressing c-Myc rescued morusin-induced inhibition of cell proliferation and tumor growth. These results suggest that morusin inhibits cell proliferation and tumor growth by down-regulating c-Myc in human gastric cancer.
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Affiliation(s)
- Feng Wang
- State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, P.R. China
| | - Dunke Zhang
- State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, P.R. China
| | - Jingxin Mao
- State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, P.R. China
| | - Xiao-Xue Ke
- State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, P.R. China
| | - Rui Zhang
- State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, P.R. China
| | - Chao Yin
- State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, P.R. China
| | - Ning Gao
- Department of Pharmacognosy, College of Pharmacy, Third Military Medical University, Chongqing, P.R. China
| | - Hongjuan Cui
- State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, P.R. China
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Abstract
Postgastrectomy syndromes result from altered form and function of the stomach. Gastrectomy disrupts reservoir capacity, mechanical digestion and gastric emptying. Early recognition of symptoms with prompt evaluation and treatment is essential. Many syndromes resolve with minimal intervention or dietary modifications. Re-operation is not common but often warranted for afferent and efferent loop syndromes and bile reflux gastritis. Preoperative nutritional assessment and treatment of common vitamin and mineral deficiencies after gastrectomy can reduce the incidence of chronic complications. An integrated team approach to risk assessment, patient education, and postoperative management is critical to optimal care of patients with gastric cancer.
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30
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Zhang J, Shi Z, Huang J, Zou X. CSTB Downregulation Promotes Cell Proliferation and Migration and Suppresses Apoptosis in Gastric Cancer SGC-7901 Cell Line. Oncol Res 2017; 24:487-494. [PMID: 28281969 PMCID: PMC7838608 DOI: 10.3727/096504016x14685034103752] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
This study aimed to investigate the pivotal role of cystatin B (CSTB) in the development of gastric cancer and to explore its possible regulatory mechanism. Human gastric cancer SGC-7901 cells as a model in vitro were transfected with plasmid PCDNA3.1-CSTB and siRNA-CSTB using Lipofectamine 2000. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to determine the relative expression of CSTB and PI3K/Akt/mTOR pathway-related protein. Moreover, MTT assay, Transwell assay, and flow cytometry were used to assess cell proliferation, migration, and apoptosis, respectively. The results showed that CSTB was significantly downregulated in SGC-7901 cells compared with gastric epithelial cells. CSTB was successfully overexpressed and suppressed after cells were transfected with pc-CSTB and si-CSTB, respectively. Moreover, cell viability and migration were significantly decreased after being transfected with pc-CSTB when compared with the control group, while being obviously increased after transfection with si-CSTB. However, cell apoptosis was significantly induced after being transfected with pc-CSTB, while being obviously suppressed after transfection with si-CSTB. Besides, the expression levels of p-PI3K, p-Akt, and p-mTOR proteins were all significantly decreased in the pc-CSTB transfection group when compared with the control group, while being increased in the si-CSTB transfection group. Our findings suggest that CSTB downregulation may promote the development of gastric cancer by affecting cell proliferation and migration, and the PI3K/Akt/mTOR signaling pathway was activated in this process. CSTB may serve as a potential therapeutic target for gastric cancer.
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Affiliation(s)
- Jian Zhang
- Department of Cancer Center, The First People's Hospital of Kashi Prefecture, Kashi Prefecture, Xinjiang, P.R. China
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31
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Dai Y, Chen X, Yin J, Kang X, Wang G, Zhang X, Nie Y, Wu K, Liang J. Investigation of injection dose and camera integration time on quantifying pharmacokinetics of a Cy5.5-GX1 probe with dynamic fluorescence imaging in vivo. JOURNAL OF BIOMEDICAL OPTICS 2016; 21:86001. [PMID: 27488591 DOI: 10.1117/1.jbo.21.8.086001] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/09/2016] [Accepted: 07/14/2016] [Indexed: 05/24/2023]
Abstract
The aim of this article is to investigate the influence of a tracer injection dose (ID) and camera integration time (IT) on quantifying pharmacokinetics of Cy5.5-GX1 in gastric cancer BGC-823 cell xenografted mice. Based on three factors, including whether or not to inject free GX1, the ID of Cy5.5-GX1, and the camera IT, 32 mice were randomly divided into eight groups and received 60-min dynamic fluorescence imaging. Gurfinkel exponential model (GEXPM) and Lammertsma simplified reference tissue model (SRTM) combined with a singular value decomposition analysis were used to quantitatively analyze the acquired dynamic fluorescent images. The binding potential (Bp) and the sum of the pharmacokinetic rate constants (SKRC) of Cy5.5-GX1 were determined by the SRTM and EXPM, respectively. In the tumor region, the SKRC value exhibited an obvious trend with change in the tracer ID, but the Bp value was not sensitive to it. Both the Bp and SKRC values were independent of the camera IT. In addition, the ratio of the tumor-to-muscle region was correlated with the camera IT but was independent of the tracer ID. Dynamic fluorescence imaging in conjunction with a kinetic analysis may provide more quantitative information than static fluorescence imaging, especially for a priori information on the optimal ID of targeted probes for individual therapy.
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Affiliation(s)
- Yunpeng Dai
- Xidian University, Engineering Research Center of Molecular and Neuro Imaging of Ministry of Education and School of Life Science and Technology, 266 Xinglong Section of Xifeng Road, Xi'an 710071, China
| | - Xueli Chen
- Xidian University, Engineering Research Center of Molecular and Neuro Imaging of Ministry of Education and School of Life Science and Technology, 266 Xinglong Section of Xifeng Road, Xi'an 710071, China
| | - Jipeng Yin
- Fourth Military Medical University, State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, 127 Changle Road, Xi'an 710032, China
| | - Xiaoyu Kang
- Fourth Military Medical University, State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, 127 Changle Road, Xi'an 710032, China
| | - Guodong Wang
- Fourth Military Medical University, State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, 127 Changle Road, Xi'an 710032, China
| | - Xianghan Zhang
- Xidian University, Engineering Research Center of Molecular and Neuro Imaging of Ministry of Education and School of Life Science and Technology, 266 Xinglong Section of Xifeng Road, Xi'an 710071, China
| | - Yongzhan Nie
- Fourth Military Medical University, State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, 127 Changle Road, Xi'an 710032, China
| | - Kaichun Wu
- Fourth Military Medical University, State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, 127 Changle Road, Xi'an 710032, China
| | - Jimin Liang
- Xidian University, Engineering Research Center of Molecular and Neuro Imaging of Ministry of Education and School of Life Science and Technology, 266 Xinglong Section of Xifeng Road, Xi'an 710071, China
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32
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Guo H, Xia B. Collapsin response mediator protein 4 isoforms (CRMP4a and CRMP4b) have opposite effects on cell proliferation, migration, and invasion in gastric cancer. BMC Cancer 2016; 16:565. [PMID: 27475326 PMCID: PMC4967517 DOI: 10.1186/s12885-016-2593-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Accepted: 07/21/2016] [Indexed: 12/04/2022] Open
Abstract
Background Collapsin response mediator proteins (CRMPs) were originally identified in the nervous system and are involved in neuronal development. Similar to CRMP1, CRMP4 has a shorter transcript encoding a short isoform known as CRMP4a, and a longer transcript encoding a long isoform known as CRMP4b. Previous studies have shown that CRMP4a and CRMP4b exhibit opposing functions in neurite outgrowth. In the present study, we aimed to determine whether CRMP4a and CRMP4b have divergent effects in gastric cancer. Methods We first analyzed the mRNA and protein expression levels of CRMP4a and CRMP4b in surgical resected specimens, gastric cancer cell lines and normal gastric epithelial cell line GES-1 by quantitative real-time PCR. Open reading frame and CRMP4b shRNA were generated by lentivirus package and stable cells stably expressing CRMP4a open reading frame and CRMP4b shRNA were constructed. Then the roles of CRMP4a and CRMP4b in cell proliferation, cell cycle progression, apoptosis, migration, invasion, and adhesion were determined by cell proliferation assays, flow cytometry analysis, transwell migration and invasion assays, cell Adhesion Assay, and tumorigenicity assays in nude mice, respectively. Results CRMP4a expression was lower and CRMP4b expression was higher in tumor tissue samples as compared to paired non-tumor tissue samples. Additionally, CRMP4a expression was lower and CRMP4b expression was higher in gastric cancer cell lines than in the normal gastric epithelial cell line GES-1. CRMP4a overexpression and CRMP4b silencing suppressed cell proliferation in vitro and in vivo. Additionally, CRMP4a overexpression and CRMP4b silencing induced a significant G1-phase arrest and a decrease of the percentage of cells in S-phase. Furthermore, CRMP4a overexpression and CRMP4b silencing inhibited cell migration, invasion, and adhesion. However, neither CRMP4a overexpression nor CRMP4b silencing affected apoptosis. Conclusion These results indicate that CRMP4a and CRMP4b have opposite effects on cell proliferation, migration, and invasion in gastric cancer.
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Affiliation(s)
- Haijian Guo
- Department of gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People's Republic of China.,Department of gastroenterology, the Second People's Hospital of Shenzhen, Shenzhen, Guangdong, 518035, People's Republic of China
| | - Bing Xia
- Department of gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People's Republic of China.
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Rosania R, Chiapponi C, Malfertheiner P, Venerito M. Nutrition in Patients with Gastric Cancer: An Update. Gastrointest Tumors 2016; 2:178-87. [PMID: 27403412 DOI: 10.1159/000445188] [Citation(s) in RCA: 78] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2016] [Accepted: 03/03/2016] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Nutritional management of patients with gastric cancer (GC) represents a challenge. SUMMARY This review provides an overview of the present evidence on nutritional support in patients with GC undergoing surgery as well as in those with advanced disease. KEY MESSAGE For patients undergoing surgery, the preoperative nutritional condition directly affects postoperative prognosis, overall survival and disease-specific survival. Perioperative nutritional support enriched with immune-stimulating nutrients reduces overall complications and hospital stay but not mortality after major elective gastrointestinal surgery. Early enteral nutrition after surgery improves early and long-term postoperative nutritional status and reduces the length of hospitalization as well. Vitamin B12 and iron deficiency are common metabolic sequelae after gastrectomy and warrant appropriate replacement. In malnourished patients with advanced GC, short-term home complementary parenteral nutrition improves the quality of life, nutritional status and functional status. Total home parenteral nutrition represents the only modality of caloric intake for patients with advanced GC who are unable to take oral or enteral nutrition. PRACTICAL IMPLICATIONS Early evaluations of nutritional status and nutritional support represent key aspects in the management of GC patients with both operable and advanced disease.
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Affiliation(s)
- Rosa Rosania
- Departments of Gastroenterology, Hepatology and Infectious Diseases, Magdeburg, Germany
| | - Costanza Chiapponi
- Departments of General, Visceral and Vascular Surgery, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - Peter Malfertheiner
- Departments of Gastroenterology, Hepatology and Infectious Diseases, Magdeburg, Germany
| | - Marino Venerito
- Departments of Gastroenterology, Hepatology and Infectious Diseases, Magdeburg, Germany
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Implications of Lymph Node Staging on Selection of Adjuvant Therapy for Gastric Cancer in the United States. Ann Surg 2016; 263:298-305. [DOI: 10.1097/sla.0000000000001360] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Xu J, Wang W, Zhu Z, Wei Z, Yang D, Cai Q. Tumor protein D52-like 2 accelerates gastric cancer cell proliferation in vitro. Cancer Biother Radiopharm 2015; 30:111-6. [PMID: 25746840 DOI: 10.1089/cbr.2014.1766] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Tumor protein D52-like 2 (TPD52L2) has been commonly described as a protein involved in tumorigenesis, according to its name. However, its pathological function remains under investigation. In the present study, TPD52L2 was found to be widely expressed in several gastric cancer cell lines. An efficient knockdown of TPD52L2 by a specific short hairpin RNA (shRNA) loaded in lentivirus resulted in a remarkable reduction in cell proliferation in both MGC80-3 and SGC-7901 cell lines with high TPD52L2 expression, but a slight or little reduction in the proliferation of MKN-28 and AGS cells with low TPD52L2 expression. Further analysis by flow cytometry revealed that the cell cycle was primarily blocked in the G0/G1 phase, especially in the sub-G1 phase by TPD52L2 silencing, implying its possible roles in cell cycle control and apoptosis. Knockdown of TPD52L2 caused a cleavage of PARP in MGC80-3 cells. Their study suggests that TPD52L2 might promote gastric carcinogenesis, and could be a promising target with respect to developing new therapeutic strategies to treat gastric cancer.
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Affiliation(s)
- Jiapeng Xu
- Department of Gastrointestinal Surgery, Changzheng Hospital, The Second Military Medical University , Shanghai, China
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Zhang ZQ, Li XJ, Liu GT, Xia Y, Zhang XY, Wen H. Identification of Annexin A1 protein expression in human gastric adenocarcinoma using proteomics and tissue microarray. World J Gastroenterol 2013; 19:7795-7803. [PMID: 24282368 PMCID: PMC3837281 DOI: 10.3748/wjg.v19.i43.7795] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2013] [Accepted: 09/17/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the differential expression of Annexin A1 (ANXA1) protein in human gastric adenocarcinoma. This study was also designed to analyze the relationship between ANXA1 expression and the clinicopathological parameters of gastric carcinoma.
METHODS: Purified gastric adenocarcinoma cells (GAC) and normal gastric epithelial cells (NGEC) were obtained from 15 patients with gastric cancer by laser capture microdissection. All of the peptide specimens were labeled as 18O/16O after trypsin digestion. Differential protein expressions were quantitatively identified between GAC and NGEC by nanoliter-reverse-phase liquid chromatography-mass/mass spectrometry (nano-RPLC-MS/MS). The expressions of ANXA1 in GAC and NGEC were verified by western blot analysis. The tissue microarray containing the expressed ANXA1 in 75 pairs of gastric carcinoma and paracarcinoma specimens was detected by immunohistochemistry (IHC). The relationship between ANXA1 expression and clinicopathological parametes of gastric carcinoma was analyzed.
RESULTS: A total of 78 differential proteins were identified. Western blotting revealed that ANXA1 expression was significantly upregulated in GAC (2.17/1, P < 0.01). IHC results showed the correlations between ANXA1 protein expression and the clinicopathological parameters, including invasive depth (T stage), lymph node metastasis (N stage), distant metastasis (M stage) and tumour-lymph node metastasis stage (P < 0.01). However, the correlations between ANXA1 protein expression and the remaining clinicopathological parameters, including sex, age, histological differentiation and the size of tumour were not found (P > 0.05).
CONCLUSION: The upregulated ANXA1 expression may be associated with carcinogenesis, progression, invasion and metastasis of GAC. This protein could be considered as a biomarker of clinical prognostic prediction and targeted therapy of GAC.
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