Protection of telomeres 1 protein levels are associated with telomere length in gastric cancer

Background: Visfatin acts as an oncogenic factor in numerous tumors through a variety of cellular processes. Visfatin has been revealed to promote cell migration and invasion in gastric cancer (GC). Snai1 is a well-known regulator of EMT process in cancers. However, the relationship between visfatin and snai1 in GC remains unclear. The current study aimed to explore the role of visfatin in GC. Methods: The RT-qPCR and western blot analysis were used to measure RNA and protein levels, respectively. The cell migration and invasion were tested by Trans-well assays and western blot analysis. Results: Visfatin showed upregulation in GC cells. Additionally, Visfatin with increasing concentration facilitated epithelial-mesenchymal transition (EMT) process by increasing E-cadherin and reducing N-cadherin and Vimentin protein levels in GC cells. Moreover, endogenous overexpression and knockdown of visfatin promoted and inhibited migratory and invasive abilities of GC cells, respectively. Then, we found that snai1 protein level was positively regulated by visfatin in GC cells. In addition, visfatin activated the NF-κB signaling to modulate snai1 protein expression. Furthermore, the silencing of snai1 counteracted the promotive impact of visfatin on cell migration, invasion and EMT process in GC. Conclusion: Visfatin facilitates cell migration, invasion and EMT process by targeting snai1 via the NF-κB signaling, which provides a potential insight for the treatment of GC.

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RUNX2 promotes malignant progression in gastric cancer by regulating COL1A1

Cancer Biomarkers ◽

10.3233/cbm-200472 ◽

2021 ◽

pp. 1-12

Author(s):

Yanlei Li ◽

Ran Sun ◽

Xiulan Zhao ◽

Baocun Sun

Keyword(s):

Gastric Cancer ◽

Human Cancer ◽

Clinical Stage ◽

Collagen Type I ◽

Migration And Invasion ◽

Type I ◽

Aberrant Expression ◽

Invasion And Migration ◽

Protein Levels

BACKGROUND: Runt-related transcription factor 2 (RUNX2) is an important gene that has been implicated in the progression of human cancer. Aberrant expression of RUNX2 predicts gastric cancer (GC) metastasis. However, the molecular mechanism of RUNX2 remains unknown. OBJECTIVE: We hypothesize that RUNX2 promotes GC metastasis by regulating the extracellular matrix component collagen type I alpha 1 (COL1A1). METHODS: The GEPIA database and immunohistochemical staining of 60 GC tissues were used to analyse the correlations between RUNX2 or COL1A1 expression and clinicopathological features, and the Kaplan-Meier method was used to evaluate survival. RT-PCR, western blotting and immunofluorescence were used to detect RUNX2 and COL1A1 expression in GC cells. Migration and invasion assays were performed to assess the influence of RUNX2 and COL1A1 on metastasis. RESULTS: RUNX2 and COL1A1 were highly expressed at both the gene and protein levels in GC, and patients who were positive for RUNX2 and COL1A1 had shorter survival. RUNX2 and COL1A1 expression linearly correlated with each other (r= 0.15, p< 0.01) and with clinical stage and lymph node metastasis (p< 0.05). Overexpressing RUNX2in vitro enhanced COL1A1 expression and promoted GC cell invasion and migration, whereas COL1A1 knockdown inhibited the increase in cell metastatic capacity promoted by RUNX2. In vivo, GC cells overexpressing RUNX2 promoted lung metastasis, and the downregulation of COL1A1 reduced the metastasis promoted by RUNX2. CONCLUSIONS: RUNX2 may promote GC metastasis by regulating COL1A1. RUNX2/COL1A1 can be employed as a novel target for therapy in GC.

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Dysregulation of ECRG4 is associated with malignant properties and of prognostic importance in human gastric cancer

Cancer Biomarkers ◽

10.3233/cbm-210334 ◽

2021 ◽

pp. 1-12

Author(s):

Yanjie You ◽

Shengjuan Hu

Keyword(s):

Gastric Cancer ◽

Prognostic Significance ◽

Statistical Analyses ◽

Human Gastric Cancer ◽

Advanced Tumor Stage ◽

Protein Levels ◽

Cancer Pathogenesis ◽

Advanced Tumor ◽

Cancer Tissues ◽

The Impact

BACKGROUND: We have previously characterized esophageal carcinoma-related gene 4 (ECRG4) as a novel tumor suppressor gene, which is frequently inactivated in nasopharyngeal carcinoma and breast cancer. Nevertheless, the expression status and prognostic significance of ECRG4 maintain elusive in human gastric cancer. Herein, we examined ECRG4 expression profile in gastric cancer and assessed its association with clinicopathological characteristics and patient survival. METHODS: Online data mining, real-time RT-PCR and immunohistochemistry were employed to determined ECRG4 expression at transcriptional and protein levels in tumors vs. noncancerous tissues. Statistical analyses including the Kaplan-Meier survival analysis and the Cox hazard model were utilized to detect the impact on clinical outcome. Moreover, ECRG4 expression was silenced in gastric cancer SGC7901 cells, and cell proliferation, colony formation and invasion assays were carried out. RESULTS: ECRG4 mRNA and protein levels were obviously downregulated in cancer tissues than noncancerous tissues. Statistical analyses demonstrated that low ECRG4 expression was found in 34.5% (58/168) of primary gastric cancer tissues, which was associated with higher histological grade (P= 0.018), lymph node metastasis (P= 0.011), invasive depth (P= 0.020), advanced tumor stage (P= 0.002) and poor overall survival (P< 0.001). Multivariate analysis showed ECRG4 expression is an independent prognostic predictor (P< 0.001). Silencing ECRG4 expression promoted gastric cancer cell growth and invasion. Western blot analysis revealed the anti-metastatic functions of ECRG4 by downregulating of E-cadherin and α-Catenin, as well as upregulating N-cadherin and Vimentin. CONCLUSIONS: Our observations reveal that ECRG4 expression is involved in gastric cancer pathogenesis and progression, and may serve as a candidate prognostic biomarker for this disease.

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Telomere length is correlated with mitochondrial DNA copy number in intestinal, but not diffuse, gastric cancer

Oncology Letters ◽

10.3892/ol.2017.6197 ◽

2017 ◽

Vol 14 (1) ◽

pp. 925-929 ◽

Cited By ~ 4

Author(s):

Soo-Jung Jung ◽

Ji-Hyoung Cho ◽

Won-Jin Park ◽

Yu-Ran Heo ◽

Jae-Ho Lee

Keyword(s):

Gastric Cancer ◽

Mitochondrial Dna ◽

Telomere Length ◽

Copy Number ◽

Diffuse Gastric Cancer ◽

Dna Copy Number ◽

Mitochondrial Dna Copy Number

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

Tumori Journal ◽

10.1177/0300891618811274 ◽

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.

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140P Preoperative and postoperative C-reactive protein levels predict recurrence and chemotherapy benefit in gastric cancer

Annals of Oncology ◽

10.1016/j.annonc.2020.10.161 ◽

2020 ◽

Vol 31 ◽

pp. S1296

Author(s):

L-L. Shen ◽

Y-H. Tang ◽

W-W. Qiu ◽

J. Lu ◽

C-H. Zheng ◽

...

Keyword(s):

Gastric Cancer ◽

C Reactive Protein ◽

Protein Levels ◽

Reactive Protein

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Activating Hippo Pathway via Rassf1 by Ursolic Acid Suppresses the Tumorigenesis of Gastric Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20194709 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4709 ◽

Cited By ~ 6

Author(s):

Seong-Hun Kim ◽

Hua Jin ◽

Ruo Yu Meng ◽

Da-Yeah Kim ◽

Yu Chuan Liu ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Cancer Cells ◽

Ursolic Acid ◽

Hippo Pathway ◽

Dependent Manner ◽

Gastric Cancer Cells ◽

Protein Levels ◽

Tumor Tissues ◽

The Hippo Pathway

The Hippo pathway is often dysregulated in many carcinomas, which results in various stages of tumor progression. Ursolic acid (UA), a natural compound that exists in many herbal plants, is known to obstruct cancer progression and exerts anti-carcinogenic effect on a number of human cancers. In this study, we aimed to examine the biological mechanisms of action of UA through the Hippo pathway in gastric cancer cells. MTT assay showed a decreased viability of gastric cancer cells after treatment with UA. Following treatment with UA, colony numbers and the sizes of gastric cancer cells were significantly diminished and apoptosis was observed in SNU484 and SNU638 cells. The invasion and migration rates of gastric cancer cells were suppressed by UA in a dose-dependent manner. To further determine the gene expression patterns that are related to the effects of UA, a microarray analysis was performed. Gene ontology analysis revealed that several genes, such as the Hippo pathway upstream target gene, ras association domain family (RASSF1), and its downstream target genes (MST1, MST2, and LATS1) were significantly upregulated by UA, while the expression of YAP1 gene, together with oncogenes (FOXM1, KRAS, and BATF), were significantly decreased. Similar to the gene expression profiling results, the protein levels of RASSF1, MST1, MST2, LATS1, and p-YAP were increased, whereas those of CTGF were decreased by UA in gastric cancer cells. The p-YAP expression induced in gastric cancer cells by UA was reversed with RASSF1 silencing. In addition, the protein levels in the Hippo pathway were increased in the UA-treated xenograft tumor tissues as compared with that in the control tumor tissues; thus, UA significantly inhibited the tumorigenesis of gastric cancer in vivo in xenograft animals. Collectively, UA diminishes the proliferation and metastasis of gastric cancer via the regulation of Hippo pathway through Rassf1, which suggests that UA can be used as a potential chemopreventive and therapeutic agent for gastric cancer.

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LncRNA H19 induced by helicobacter pylori infection promotes gastric cancer cell growth via enhancing NF-κB-induced inflammation

Journal of Inflammation ◽

10.1186/s12950-019-0226-y ◽

2019 ◽

Vol 16 (1) ◽

Cited By ~ 2

Author(s):

Yifeng Zhang ◽

Jin Yan ◽

Chao Li ◽

Xiaoyong Wang ◽

Yu Dong ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Cell Growth ◽

Migration And Invasion ◽

Cancer Cell Growth ◽

Protein Levels ◽

Non Coding Rna ◽

Healthy Donors ◽

H Pylori ◽

Long Non Coding Rna

Abstract Background The aim of this study was to investigate the role of long non-coding RNA (lncRNA) H19 in gastric cancer (GC) with Helicobacter pylori (H. pylori). Methods H19 expression in peripheral blood from H. pylori+/− GC patients and healthy donors (control) as well as in GC tissues and cells were detected by qRT-PCR. Cell proliferation was evaluated by CCK-8 assay. Cell migration and invasion were evaluated by Transwell assay. The levels of pro-inflammatory cytokines were determined by ELISA. The protein levels of IκBα, p-IκBα and p65 were determined by western blotting. Results H19 expression was upregulated in H. pylori-infected GC tissues and cells. Furthermore, H. pylori promoted GC cell viability, migration, invasion and inflammatory response. Moreover, H19 overexpression promoted the proliferation, migration and invasion of H. pylori-infected GC cells via enhancing NF-κB-induced inflammation. Conclusions LncRNA H19 promotes H. pylori-induced GC cell growth via enhancing NF-κB-induced inflammation.

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DUOX2 Expression Is Increased in Barrett Esophagus and Cancerous Tissues of Stomach and Colon

Gastroenterology Research and Practice ◽

10.1155/2016/1835684 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 8

Author(s):

Ran Qi ◽

Yunfeng Zhou ◽

Xiaozhen Li ◽

Hong Guo ◽

Lei Gao ◽

...

Keyword(s):

Gastric Cancer ◽

Barrett Esophagus ◽

Smoking History ◽

Clinicopathological Parameters ◽

Mrna Levels ◽

Hepatic Carcinoma ◽

Normal Epithelium ◽

Real Time Quantitative Pcr ◽

Protein Levels ◽

Normal Tissues

Aim. To detect the expression of dual oxidase (DUOX) 2 in Barrett esophagus, gastric cancer, and colorectal cancer (CRC).Materials and Methods. The endoscopic biopsies were collected from patients with Barrett esophagus, while the curative resection tissues were obtained from patients with gastric cancer, CRC, or hepatic carcinoma. The DUOX2 protein and mRNA levels were detected with immunohistochemistry (IHC) and real-time quantitative PCR (qPCR). The correlation of DUOX2 expression with clinicopathological parameters of tumors was identified.Results. Low levels of DUOX2 mRNA were detected in Barrett esophagus and the adjacent normal tissues, and there was no difference between these two groups. DUOX2 protein was found in Barrett esophagus and undetectable in the normal epithelium. The DUOX2 mRNA and protein levels in the gastric cancer and CRC were increased compared to the adjacent nonmalignant tissues. The elevated DUOX2 in the gastric cancer was significantly associated with smoking history. In CRC tissues, the DUOX2 protein expression level in stages II–IV was significantly higher than that in stage I. In both hepatic carcinoma and the adjacent nonmalignant tissue, the DUOX2 was virtually undetectable.Conclusion. DUOX2 in Barrett esophagus, gastric cancer, and CRC may be involved in the tumorigenesis of these tissues.

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