scholarly journals The Functional Variant in the 3'UTR of IGF1 with the Risk of Gastric Cancer in a Chinese Population

2015 ◽  
Vol 36 (3) ◽  
pp. 884-892 ◽  
Author(s):  
Haiqiang Jiang ◽  
Huiyun Wang ◽  
Fengyuan Ge ◽  
Lamei Wu ◽  
Xiao Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Chinese Population ◽  
Human Cancer ◽  
Luciferase Reporter ◽  
Human Gastric Cancer ◽  
Genotype Assay ◽  
Endocrine Hormone ◽  
Study Results ◽  
Functional Variant

Background/Aims: IGF-1 can act as an endocrine hormone and its signaling server as essential roles in regulating tumorigenesis. Polymorphisms in IGF-1 have been reported associated bad prognosis of with human cancer, but their association with the risk of human gastric cancer (GC) has not been found so far. In this study rs6218 located in the 3'UTR of IGF-1 was selected to evaluate its relationship with the risk of GC among Chinese population. Methods: Questionnaire, SNaPshot genotype assay, real time PCR assay, cell transfection and the dual luciferase reporter assay were used in our study. Results: SNP rs6218 in IGF-1 3'-UTR was involved in the occurrence of GC by acting as a tumor promotion factor while rs6128 acting as a risk factor. SNP rs6128 was also could be regulated by miR-603 which caused an up-regulation of IGF-1 in patients with UC and CC genotype. Furthermore, the carriers of UC and CC genotype presented a big tumor size as well as the high probability of metastasis. Conclusion: In conclusion, our findings have shown that the SNP rs6218 in IGF-1 3'-UTR, through disrupting the regulatory role of miR-603 in IGF-1 expression, rs16128 in IGF-1 might act as a promotion factor in the pathogenesis of GC.

scholarly journals MicroRNA-219-5p Represses the Proliferation, Migration, and Invasion of Gastric Cancer Cells by Targeting the LRH-1/Wnt/β-Catenin Signaling Pathway

2017 ◽  
Vol 25 (4) ◽  
pp. 617-627 ◽  
Author(s):  
Chunsheng Li ◽  
Jingrong Dong ◽  
Zhenqi Han ◽  
Kai Zhang
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Human Cancer ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Cancer Tissues

MicroRNAs (miRNAs) are reportedly involved in gastric cancer development and progression. In particular, miR-219-5p has been reported to be a tumor-associated miRNA in human cancer. However, the role of miR-219-5p in gastric cancer remains unclear. In this study, we investigated for the first time the potential role and underlying mechanism of miR-219-5p in the proliferation, migration, and invasion of human gastric cancer cells. miR-219-5p was found to be markedly decreased in gastric cancer tissues and cell lines compared with adjacent tissues and normal gastric epithelial cells. miR-219-5p mimics or anti-miR-219-5p was transfected into gastric cancer cell lines to overexpress or suppress miR-219-5p expression, respectively. Results showed that miR-219-5p overexpression significantly decreased the proliferation, migration, and invasion of gastric cancer cells. Conversely, miR-219-5p suppression demonstrated a completely opposite effect. Bioinformatics and luciferase reporter assays indicated that miR-219-5p targeted the 3′-untranslated region of the liver receptor homolog-1 (LRH-1), a well-characterized oncogene. Furthermore, miR-219-5p inhibited the mRNA and protein levels of LRH-1. LRH-1 mRNA expression was inversely correlated with miR-219-5p expression in gastric cancer tissues. miR-219-5p overexpression significantly decreased the Wnt/β-catenin signaling pathway in gastric cancer cells. Additionally, LRH-1 restoration can markedly reverse miR-219-5p-mediated tumor suppressive effects. Our study suggests that miR-219-5p regulated the proliferation, migration, and invasion of human gastric cancer cells by suppressing LRH-1. miR-219-5p may be a potential target for gastric cancer therapy.

Role of aurora kinase A on regulating inflammation and inducing NF-κB pathway activation in gastric cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 78-78
Author(s):  
Ahmed M. Katsha ◽  
Vikas Sehdev ◽  
Mohammed Soutto ◽  
DunFa Peng ◽  
Abbes Belkhiri ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Target Genes ◽  
Aurora Kinase ◽  
Luciferase Reporter ◽  
Human Gastric Cancer ◽  
Nuclear Staining ◽  
Aurora Kinase A ◽  
Kinase A

78 Background: Aurora kinase A gene (AURKA) is frequently amplified and/or overexpressed in several malignancies. Inflammation contributes to the pathogenesis of gastric tumorigenesis. We explored the roles of AURKA in inflammation and tumorigenesis. Methods: Immunofluorescence, immunohistochemistry, Quantitative real-time PCR, immunoblot, co-immunoprecipitation, luciferase reporter, and in vitro kinase assays were used to analyze AGS and MKN28 gastric cancer cells. We also analyzed Tff1–/– mice, growth of tumor xenografts, and human tissues. Results: We showed an elevated level of AURKA in the Tff1–/– gastric tissues as compared to wild-type. We also found a positive correlation between AURKA and inflammation (coefficient r = 0.25; P = 0.0056) as well as TNF-α (coefficient r = 0.25; P = 0.0057). AURKA inhibition by MLN8237, a specific AURKA inhibitor, reduced nuclear staining of NFκB in human gastric cancer samples and mouse epithelial cells, suppressed NFκB reporter activity, and reduced the expression of NFκB target genes that regulate inflammation and cell survival. Additionally, AURKA inhibition reduced xenograft tumor size in mice and reversed the development of gastric tumors in Tff1–/– mice. Further, we found that AURKA regulate NFκB activity by directly binding and phosphorylating IκBα in vitro. Premalignant and malignant lesions from the gastric mucuosa of patients had increased levels of AURKA protein and nuclear NFκB, compared with healthy gastric tissue. Conclusions: In analyses of gastric cancer cell lines, human tissue samples, and mouse models, we found AURKA to be upregulated during chronic inflammation to promote IκBα-mediated activation of NFκB and tumorigenesis. This provides a novel role of AURKA in cancer and shows the importance of targeting it as a therapeutic approach in cancer treatment.

Essential role of Her3 in two signaling transduction patterns: Her2/Her3 and MET/Her3 in proliferation of human gastric cancer

2014 ◽  
Vol 54 (12) ◽  
pp. 1700-1709 ◽  
Author(s):  
Chen Yun ◽  
Li Gang ◽  
Gu Rongmin ◽  
Wen Xu ◽  
Ming Xuezhi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Essential Role ◽  
Human Gastric Cancer ◽  
Signaling Transduction

6650 Myc-dependent regulation and prgonostic role of Myc stabilizing protein, CIP2A, in human gastric cancer

2009 ◽  
Vol 7 (2) ◽  
pp. 403 ◽  
Author(s):  
A. Khanna ◽  
C. Böckelman ◽  
J. Westermarck ◽  
A. Ristimäki
Keyword(s):  
Gastric Cancer ◽  
Human Gastric Cancer

scholarly journals BAG3 contributes to HGF-mediated cell proliferation, migration, and invasion via the Egr1 pathway in gastric cancer

2018 ◽  
Vol 105 (1) ◽  
pp. 63-75
Author(s):  
Jae Chang Lee ◽  
Sung Ae Koh ◽  
Kyung Hee Lee ◽  
Jae-Ryong Kim
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Invasion ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Protein Levels ◽  
Dependent Pathway

Introduction: Bcl2-associated athanogene 3 (BAG3) is elevated in several types of cancers. However, the role of BAG3 in progression of gastric cancer is unknown. Therefore, the present study aims to find out the role of BAG3 in hepatocyte growth factor (HGF)–mediated tumor progression and the molecular mechanisms by which HGF regulates BAG3 expression. Methods: BAG3 mRNA and protein were measured using reverse transcription polymerase chain reaction and Western blot in the 2 human gastric cancer cell lines, NUGC3 and MKN28, treated with or without HGF. The effects of BAG3 knockdown on cell proliferation, cell invasion, and apoptosis were analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the in vitro 2-chamber invasion assay, and flow cytometry in BAG3 short hairpin RNA (shRNA)–transfected cells and control cells. The signaling pathways involved in BAG3 that are regulated by HGF were analyzed. The chromatin immunoprecipitation assay was used to determine binding of Egr1 to the BAG3 promoter. Results: BAG3 mRNA and protein levels were increased following treatment with HGF. HGF-mediated BAG3 upregulation increased cell proliferation and cell invasion; however, it decreased apoptosis. HGF-mediated BAG3 upregulation is regulated by an ERK and Egr1-dependent pathway. BAG3 may have an important role in HGF-mediated cell proliferation and metastasis in gastric cancer through an ERK and Egr1-dependent pathway. Conclusion: This pathway may provide novel therapeutic targets and provide information for further identification of other targets of therapeutic significance in gastric cancer.

scholarly journals Hypermethylation of DHRS3 as a Novel Tumor Suppressor Involved in Tumor Growth and Prognosis in Gastric Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Sha Sumei ◽  
Kong Xiangyun ◽  
Chen Fenrong ◽  
Sun Xueguang ◽  
Hu Sijun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Suppressor ◽  
Tumor Growth ◽  
Human Cancer ◽  
Methylation Status ◽  
Ectopic Expression ◽  
Survival Times

Background/AimsThe role of DHRS3 in human cancer remains unclear. Our study explored the role of DHRS3 in gastric cancer (GC) and its clinicopathological significance and associated mechanisms.MaterialsBisulfite-assisted genomic sequencing PCR and a Mass-Array system were used to evaluate and quantify the methylation levels of the promoter. The expression levels and biological function of DHRS3 was examined by both in vitro and in vivo assays. A two-way hierarchical cluster analysis was used to classify the methylation profiles, and the correlation between the methylation status of the DHRS3 promoter and the clinicopathological characteristics of GC were then assessed.ResultsThe DHRS3 promoter was hypermethylated in GC samples, while the mRNA and protein levels of DHRS3 were significantly downregulated. Ectopic expression of DHRS3 in GC cells inhibited cell proliferation and migration in vitro, decreased tumor growth in vivo. DHRS3 methylation was correlated with histological type and poor differentiation of tumors. GC patients with high degrees of CpG 9.10 methylation had shorter survival times than those with lower methylation.ConclusionDHRS3 was hypermethylated and downregulated in GC patients. Reduced expression of DHRS3 is implicated in gastric carcinogenesis, which suggests DHRS3 is a tumor suppressor.

scholarly journals Has-miR-875-5p Inhibits Tumorigenesis by Targeting USF2 via TGF-β Signaling Pathway in Gastric Cancer

2021 ◽  
Author(s):  
Shenshuo Gao ◽  
Zhikai Zhang ◽  
Xubin Wang ◽  
Yan Ma ◽  
Chensheng Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Research Direction ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
New Research

Abstract Background: Gastric cancer (GC) is one of the most common malignancies, and more and more evdiences show that the pathogenesis is regulated by various miRNAs.In this study, we investigated the role of miR-875 in GC. Methods:The expression of miR-875-5p was detected in human GC specimens and cell lines by miRNA RT-PCR. The effect of miR-875-5p on GC proliferation was determined by CCK-8 proliferation assay and EDU assay. Migration and invasion were examined by transwell migration and invasion assay and wound healing assay. The interaction between miR-875-5p and its target gene USF2 was verified by a dual luciferase reporter assay. The effects of miR-875-5p in vivo were studied in xenograft nude mice models.Related proteins were detected by Western blot.Results:The results showed that miR-875-5p inhibited the proliferation, migration and invasion of gastric cancer cells in vitro, and inhibited tumorigenesis in vivo. USF2 proved to be a direct target of miR-875-5p. Knockdown of USF2 partially counteracts the effects of miR-875-5p inhibitors.Overexpression of miR-875-5p can inhibit proliferation, migration, and invasion through the TGF-β signaling pathway by down-regulation of USF2 in GC, providing a new research direction for the diagnosis and targeted therapy of GC.Conclusions: MiR-875-5pcan inhibited the progression of GC by directly targeting USF2 and negatively regulating TGF-β signaling pathway.In the future, miR-875-5p is expected to be used as a potential therapeutic target for GC therapy.

scholarly journals Role of PCDH10 and its hypermethylation in human gastric cancer

2012 ◽  
Vol 1823 (2) ◽  
pp. 298-305 ◽  
Author(s):  
Zesong Li ◽  
James C.S. Chim ◽  
Mo Yang ◽  
Jieyu Ye ◽  
Benjamin C.Y. Wong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Human Gastric Cancer

scholarly journals Genetic Variants in the 3′ Untranslated Region of sFRP1 Gene and Risk of Gastric Cancer in a Chinese Population

2017 ◽  
Vol 32 (1) ◽  
pp. 102-107
Author(s):  
Juan Wu ◽  
Junfeng Zhang ◽  
Qinhong Cao ◽  
Junqin Wang ◽  
Zhen Zhan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Risk ◽  
Genetic Variants ◽  
Chinese Population ◽  
Untranslated Region ◽  
Wnt Signaling Pathway ◽  
Negative Regulator ◽  
Polymorphism Analysis ◽  
Human Gastric Cancer ◽  
The Impact

Background Secreted frizzled-related protein 1 (sFRP1), a negative regulator of the Wnt signaling pathway, is frequently inactivated in human gastric cancer. Genetic variants in the 3′ untranslated region (UTR) of the gene may influence the strength of miRNA binding and the regulation of mRNA transcription, affecting the individual's cancer risk. This study aims to investigate the impact of variants in the 3′ UTR of sFRP1 on the gastric cancer susceptibility in a Chinese population. Patients and methods The association between 2 sFRP1 gene variation loci (rs1127379 and rs10088390) with minor allele frequency more than 0.1 in the 3′ UTR and gastric cancer risk was assessed in a case-control study including 419 gastric cancer cases and 571 healthy controls. PCR-restriction fragment length polymorphism analysis was used for genotyping; the odds ratio and 95% confidence interval were calculated to estimate the relative risk. Results Compared with the AA genotype, the GG genotype of rs1127379 was significantly associated with a reduced risk of gastric cancer overall. In the subgroup analysis, the protective effect of the GG genotype was also found for noncardia cancer and intestinal gastric cancer. Furthermore, haplotype analysis showed that the Ars1127379 Grs10088390 haplotype conferred a risk effect for gastric cancer. Conclusions Genetic variants at the sFRP1 gene may be involved in gastric tumorigenesis, especially in noncardia and intestinal gastric cancer. Further prospective studies with different ethnicities and large sample sizes are needed to confirm our findings.

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