Annona cherimola is a tree belonging to the family Annonacea, whose fruit (cherimoya) is very desirable, but its seeds are considered waste. Present in these seeds are compounds that have been described as selective antiproliferative agents for cancer cells. The aim of this study was to evaluate the antiproliferative activity of ethanol macerate extract (EMCHS) obtained from A. cherimola seeds against the human stomach gastric adenocarcinoma (AGS) cell line and the normal human gastric epithelial cell line (GES-1). The EMCHS extract presented an IC

Angiogenesis is recognized as a sign of cancer and facilitates cancer progression and metastasis. Suppression of angiogenesis is a desirable strategy for gastric cancer (GC) management. In this study, we showed a novel role of gastrin in angiogenesis of GC. We observed that treatment with gastrin 17 (G17) increased the proliferation of AGS cells and enhanced tube formation during normoxia and hypoxia. The expression level of VEGF were increased by G17 treatment as well. Experiments on the mechanism showed that G17 promoted HIF-1α expression, which subsequently enhanced β-catenin nuclear localization and activation of TCF3 and LEF1 and finally resulted in angiogenesis by upregulating VEGF. An in vivo experiment confirmed that G17 enhanced GC cell proliferation and angiogenesis in the resultant tumor. In conclusion, our findings indicate that gastrin promotes angiogenesis via activating HIF-1α/β-catenin/VEGF axis in GC.

Gastric cancer (GC) is a leading cause of cancer‑associated mortality worldwide. Previous studies demonstrated that long noncoding RNAs (lncRNAs) may be dysregulated in GC and may serve important roles in cancer progression. The present study aimed to investigate the role of the novel lncRNA stomach cancer‑associated transcript 16 (STCAT16; Assembly Gene ID G038291) in the development and progression of GC. The present data suggested that the expression level of STCAT16 was decreased in GC tissues. The expression level of STCAT16 was identified to be associated with lymph node and tumour node metastasis stages. Furthermore, the expression level of STCAT16 was identified to be significantly associated with poor survival and prognosis. Knockdown of STCAT16 promoted proliferation, colony formation, migration and invasion of BGC‑823 cells. In contrast, these features were suppressed in AGS cells following overexpression of STCAT16. In vivo, tumour growth was significantly decreased following STCAT16 overexpression. Collectively, the present data suggested that the lncRNA STCAT16 may act as a tumour suppressor and may inhibit GC tumour cell growth and migration. Additionally, the decreased expression level of STCAT16 was identified to be associated with poor prognosis in patients with GC.

AIMS: Identifying alterations in lipid metabolism along gastric adenocarcinoma (GA) tumorigenesis pathways could lead to a new approach for potential diagnosis, efficient prediction and promising therapeutic strategies. This study aimed to identify the possible effect of HIF-1α on FASN and SREBP-1c regulation in GA.
MAIN METHODS: AGS cell line was cultured in normoxic and hypoxic conditions, and HIF-1α, FASN and SREBP-1c gene expression were analyzed by qRT-PCR and Western blot. Serum HIF-1α, FASN and insulin concentration were measured in 112 GA patients and 156 control cases by ELISA, and immunohistochemical method was employed to analyze SREBP-1c expression. Tissue mRNA expression of SREBP-1c, FASN and HIF-1α were determined by qRT-PCR.
KEY FINDINGS: In vitro findings indicate upregulation of HIF-1α, FASN and SREBP-1c gene and protein expression in the hypoxic culture of AGS cells. High circulating levels of HIF-1α and FASN were significantly observed in GA patients compared to the controls. HIF-1α, SREBP-1c and FASN gene expression were higher in GA vs. controls. In addition, SREBP-1c protein level was enhanced in GA tissues compared to controls. Furthermore, elevated serum levels of HIF-1α and FASN and expression of HIF-1α, SREBP-1c and FASN genes were associated with unfavorable clinicopathological features such as diffuse type tumor and poor survival.
SIGNIFICANCE: The results by correlating increased levels of FASN to those of HIF-1α and SREBP-1c are consistent with a possible up-regulation of FASN upon induction of HIF-1α through SREBP-1c.

Naphthalene diimide (NDI) derivatives have been shown to exhibit promising antineoplastic properties. In the current study, we assessed the anticancer and anti-bacterial properties of di-substituted NDI derivative. The naphthalene-bis-hydrazimide, 1, negatively affected the cell viability of three cancer cell lines (AGS, HeLa and PC3) and induced S phase cell cycle arrest along with SubG0/G1 accumulation. Amongst three cell lines, gastric cancer cell line, AGS, showed the highest sensitivity towards the NDI derivative 1. Compound 1 induced extensive DNA double strand breaks causing p53 activation leading to transcription of p53 target gene p21 in AGS cells. Reduction in protein levels of p21 and BRCA1 suggested that 1 treated AGS cells underwent cell death due to accumulation of DNA damage as a result of impaired DNA damage repair. β-catenin downregulation and consequently decrease in levels of c-Myc may have led to 1 induced AGS cell proliferation inhibition.1 induced AGS cell S phase arrest was mediated through CylinA/CDK2 downregulation. The possible mechanisms involved in anticancer activity of 1 includes ROS upregulation, induction of DNA damage, disruption of mitochondrial membrane potential causing ATP depletion, inhibition of cell proliferation and downregulation of antiapoptotic factors ultimately leading to mitochondria mediated apoptosis. Further compound 1 also inhibited H. pylori proliferation as well as H. pylori induced morphological changes in AGS cells. These findings suggest that NDI derivative 1 exhibits two-pronged anticancer activity, one by directly inhibiting cancer cell growth and inducing apoptosis and the other by inhibiting H. pylori.

BACKGROUND Gastric cancer is a common gastrointestinal tumor. The incidence and mortality of gastric cancer are very high. Therefore, it is important to study targeted drugs. Recent studies found long chain non-coding RNA (lncRNAs) and microRNAs (miRNAs) were abnormal in gastric cancer. MATERIAL AND METHODS We collected adjacent normal and cancer tissues of gastric cancer patients and measured HOTAIR, miR-454-3p, STAT3, and Cyclin D1 expression and analyzed the correlation with clinical status. We also measured AGS and SGC7901 cells proliferation rate of different groups by MTT assay, and we evaluated AGS and SGC7901 cell apoptosis and cell cycle by flow cytometry. In addition, we assessed the relative proteins expressions by WB assay. Finally, we explored the correlation between miR-454-3p and STAT3 by use of double luciferase reporter. RESULTS lncRNA HOTAIR was negatively correlated with miR-454-3p expression in gastric cancer tissues. lncRNA HOTAIR knockdown suppressed AGS and SGC7901, which are gastric cancer cell lines that promote cell proliferation by increasing cell apoptosis and keeping the cell cycle in G1 phase. In further mechanism research, we found that the STAT3 and Cyclin D1 proteins expressions were suppressed by lncRNA HOTAIR down-regulation in AGS and SGC7901 cells. CONCLUSIONS Our results suggest that lncRNA HOTAIR knockdown stimulates miR-454-3p expression to inhibit gastric cancer growth by depressing STAT3/Cyclin D1 activity.

Cancer tissues contain small populations of highly tumorigenic cells termed cancer stem cells (CSCs). Immortalized cell lines containing CSCs are valuable and powerful experimental tools for research into the characteristics of these stem cells. We previously reported that the hepatocellular carcinoma cell line Li-7 includes abundant CD13

The present study aimed to explore the possible effects of membrane‑type 1 matrix metalloproteinase (MT1‑MMP) on gastric carcinoma cells proliferation and invasion. Immunohistochemistry analysis was conducted to measure MT1‑MMP expression level in 15 patients with gastric carcinoma. Subsequently, recombinant short hairpin RNA (shRNA) vectors targeting MT1‑MMP were constructed to silence the expression of MT1‑MMP in gastric carcinoma cells. Then, the inhibitive efficiency was verified via reverse transcription quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis. The effects of MT1‑MMP silencing on cell proliferation and invasion were detected through Cell Counting Kit‑8 test and Transwell assays. The expression levels of vimentin and epithelial cadherin (E‑cadherin) were detected by RT‑qPCR. The immunohistochemistry analysis results revealed that MT1‑MMP expression in gastric carcinoma tissues was markedly overexpressed compared with non‑cancerous adjacent tissues. The MT1‑MMP expression level in cancer‑derived cell line AGS cells was also significantly increased compared with that in non‑cancer‑derived GES‑1 cells. In addition, the MT1‑MMP expression level in AGS cells was significantly decreased via shRNA transfection. Cell proliferation and invasion were markedly inhibited following knockdown of MT1‑MMP level in AGS cells. These inhibitory effects were associated with the decreased expression of vimentin and increased expression of E‑cadherin. MT1‑MMP was overexpressed in gastric carcinoma cells, and silencing of MT1‑MMP inhibited the proliferation and invasion of cells via regulating the expression of vimentin and E‑cadherin.

BP‑1‑102, a novel inhibitor of signal transducer and activator of transcription 3 (STAT3), exhibits significant antitumor effects in several malignancies in vitro and in vivo. However, its role in gastric cancer (GC) remains to be elucidated. In the present study, the effect and potential molecular mechanisms of BP‑102 in human GC cell lines were investigated. The results showed that BP‑1‑02 dose‑dependently inhibited the proliferation of AGS cells, whereas it had little effect on HGC‑27 cells. Flow cytometric analysis indicated that BP‑1‑102 induced apoptosis, but had minimal effect on cell cycle distribution. In addition, cells treated with BP‑1‑102 demonstrated markedly suppressed migration and invasion capacities. Western blot analysis revealed that BP‑1‑102 inhibited the phosphorylation of STAT3 and its target genes, including c‑Myc, cyclin D1 and survivin, in a time‑ and dose‑dependent manner. Furthermore, it was found that BP‑1‑102 induced the phosphorylation of c‑Jun N‑terminal kinase and p38 mitogen‑activated protein kinase (MAPK) and inhibited the activation of extracellular signal‑related kinases. Taken together, these results demonstrated that BP‑1‑102 may be a potent antitumor agent that acts through modulating the STAT3 and MAPK signaling pathways in GC cells.

Metformin is commonly used to treat patients with type 2 diabetes and is associated with a decreased risk of cancer. Previous studies have demonstrated that metformin can act alone or in synergy with certain anticancer agents to achieve anti‑neoplastic effects on various types of tumors via adenosine monophosphate‑activated protein kinase (AMPK) signaling. However, the role of metformin in AMPK‑mediated apoptosis of human gastric cancer cells is poorly understood. In the current study, metformin exhibited a potent anti‑proliferative effect and induced apoptotic characteristics in human AGS gastric adenocarcinoma cells, as demonstrated by MTT assay, morphological observation method, terminal deoxynucleotidyl transferase dUTP nick end labeling and caspase‑3/7 assay kits. Western blot analysis demonstrated that treatment with metformin increased the phosphorylation of AMPK, and decreased the phosphorylation of AKT, mTOR and p70S6k. Compound C (an AMPK inhibitor) suppressed AMPK phosphorylation and significantly abrogated the effects of metformin on AGS cell viability. Metformin also reduced the phosphorylation of mitogen‑activated protein kinases (ERK, JNK and p38). Additionally, metformin significantly increased the cellular ROS level and included loss of mitochondrial membrane potential (ΔΨm). Metformin altered apoptosis‑associated signaling to downregulate the BAD phosphorylation and Bcl‑2, pro‑caspase‑9, pro‑caspase‑3 and pro‑caspase‑7 expression, and to upregulate BAD, cytochrome c, and Apaf‑1 proteins levels in AGS cells. Furthermore, z‑VAD‑fmk (a pan‑caspase inhibitor) was used to assess mitochondria‑mediated caspase‑dependent apoptosis in metformin‑treated AGS cells. The findings demonstrated that metformin induced AMPK‑mediated apoptosis, making it appealing for development as a novel anticancer drug for the treating gastric cancer.

Background/Aims: This study aimed to explore the effect of circular RNA ARHGAP26 (circ-ARHGAP26) on cell proliferation and apoptosis in gastric cancer (GC) cell lines.
Materials and Methods: Human GC cell lines including HGC-27, AGS, SGC-7901, BGC-823, NCI-N87 and human normal gastric mucosal cells GSE-1 were cultured. The circ-ARHGAP26 expression was determined by quantitative polymerase chain reaction assay. Blank inhibitor and circ-ARHGAP26 inhibitor plasmids were transfected into HGC-27 or AGS cells as NC (-) and circ-ARHGAP26(-) groups. Counting Kit-8 (CCK-8) and Annexin V (AV)/propidium iodide (PI) were conducted to evaluate cell proliferation and cell apoptosis, respectively. Western blot was performed to determine the expressions of apoptotic markers (C-Caspase3 and Bcl-2).
Results: The circ-ARHGAP26 expression was elevated in HGC-27 (P < 0.001), AGS (P < 0.001), SGC-7901 (P < 0.01), BGC-823 (P < 0.05) and NCI-N87 (P < 0.05) GC cell lines compared to GSE-1 cells. In HGC-27 cells, CCK8 assay revealed that cell proliferation was decreased at 48 h (P < 0.05) and 72 h (P < 0.01), while AV/PI assay disclosed that cell apoptosis rate was increased at 72 h in circ-ARHGAP26 (-) group compared to NC (-) group (P < 0.01). Western blot assay also illuminated that apoptotic marker C-Caspase 3 was raised, while anti-apoptotic marker Bcl-2 was reduced at 72 h in circ-ARHGAP26 (-) group compared to NC (-) group. In addition, further validation in AGS cells also exhibited that cells proliferation was repressed, while apoptosis was enhanced in circ-ARHGAP26 (-) group compared to NC (-) group.
Conclusion: The circ-ARHGAP26 is over-expressed and its downregulation inhibits cell proliferation and promotes cells apoptosis in GC cells.

Circular RNAs (circRNAs) are a novel class of non-coding RNA molecules in eukaryotic organisms that have potentially important roles in gene regulation. Nevertheless, whether viruses can encode circRNA is still uncertain. To examine whether large genome DNA viruses can generate circRNA during the infection of human cells, we performed RNA sequencing of ribosomal RNA-depleted total RNA from Epstein-Barr virus (EBV)-infected cell lines, including SNU-719, AGS-EBV, C666-1 and Akata. We identified an EBV-encoded circRNA, ebv_circ_RPMS1, that consists of the head-to-tail splicing of exons 2-4 from the RPMS1 gene. Furthermore, we demonstrated that ebv_circ_RPMS1 was localized in both cytoplasm and nuclei. Given that circRNAs shape gene expression by titrating microRNAs, regulating transcription and/or interfering with splicing, we identified a novel viral regulator of host and/or viral gene expression.

Acquired drug resistance is one of the main limitations in pharmacological therapy of malignancies including gastric cancer. MicroRNAs (miRNAs) are a class of small noncoding RNAs that suppress their targets by binding to the 3'UTR region of genes. In this study, we explored investigate the target gene of miR-494 and its roles in chemoresistance of gastric cancer. We found that miR-494 was significantly down-regulated in gastric cancer cells lines compared to the normal gastric epithelial cell line. Exogenous overexpression of miR-494 increased the chemosensitivity of gastric cancer cells to doxorubicin. Moreover, miR-494 expression was reduced in a doxorubicin-resistant gastric cancer cells (AGS/dox) compared with the parental cells. MTT assay showed that AGS/dox cells exhibited an elevated viability compared with the parental cells. Enforced expression of miR-494 inhibited AGS/dox cell viability and colony formation ability. In addition, we demonstrated that elevated expression of miR-494 inhibited the mRNA and protein expression of phosphodiesterases 4D (PDE4D) in gastric cancer cell. Luciferase assay showed that miR-494 directly targeted the 3'UTR region of PDE4D. Furthermore, restoration of PDE4D recovered the chemoresistance in miR-494-overexpressed gastric cancer cells. Taken together, this study demonstrated that miR-494 enhanced doxorubicin sensitivity via regulation of PDE4D expression, suggesting a novel therapeutic strategy for anti-chemoresistance in gastric cancer.

BACKGROUND Long noncoding RNAs (lncRNAs) are important regulators in human disease, including cancers. LncRNA MIR22HG has been shown to inhibit the progression of endometrial carcinoma, lung cancer, and hepatocellular carcinoma. Its role in gastric cancer is unclear. This study investigated MIR22HG effects on gastric cancer. MATERIAL AND METHODS Gastric cancer tissues (n=43) and adjacent normal tissues (n=21) were collected. Patients' 5-year overall survival rate was analyzed. Human normal gastric mucosal cell line (GES-1) and gastric cancer cell lines (MKN-45, AGS, SGC-7901) were cultured. AGS and MKN-45 cells were transfected by pcDNA3 empty vector, pcDNA3-MIR22HG overexpression vector, MIR22HG siRNA and its negative control, NOTCH2 siRNA and its negative control, respectively. Proliferation was explored by CCK-8 assay. Migration and invasion were explored by Transwell. qRT-PCR and western blot were used to investigate mRNA and proteins expression, respectively. RESULTS MIR22HG expression was decreased in gastric cancer tissues and cells (P<0.05). Low MIR22HG expression indicated lower 5-year overall survival rate (P<0.05). Upregulation of MIR22HG inhibited AGS and MKN-45 cell proliferation, migration and invasion (all P<0.05). Downregulation of MIR22HG elevated AGS and MKN-45 cell proliferation, migration, and invasion (all P<0.05). MIR22HG negatively regulated NOTCH2 signaling. Silencing MIR22HG elevated HEY1 and nucleus NOTCH2 expression. Silencing of NOTCH2 suppressed AGS and MKN-45 cells proliferation, migration and invasion (all P<0.05). CONCLUSIONS LncRNA MIR22HG suppressed gastric cancer progression through attenuating NOTCH2 signaling.

Hyperlipidemia is associated with metastasis in patients with gastric cancer (GC). 25‑Hydroxycholesterol (25‑HC) is a type of oxysterol which is synthesized from cholesterol and is involved in a number of processes, including inflammation, immune responses and cancer development. However, the role of 25‑HC in gastric cancer remains unknown. In the present study, we demonstrated that 25‑HC had no effects on GC cell proliferation and apoptosis, whereas it decreased the sensitivity of GC cells to 5‑fluorouracil (5‑FU), as demonstrated by the increased cell proliferation and the decreased cell apoptosis. On the other hand, exposure to 2.5‑10 µM of 25‑HC significantly promoted GC invasion, both in vitro (using AGS and MGC‑803 GC cell lines) and in vivo (in an animal model), accompanied by the upregulation of the expression levels of matrix metalloproteinases (MMPs). Further investigations revealed that the promotion of GC invasion was, at least in part due to the activation of Toll‑like receptor 2 (TLR2)/nuclear factor (NF)‑κB signaling. Our results demonstrated that 25‑HC promoted GC cells invasion by upregulating TLR2/NF‑κB‑mediated MMP expression. Thus, on the whole, the findings of this study suggest a novel mechanism of hyperlipidemia‑induced GC progression.

BACKGROUND: Lipopolysaccharide (LPS) from Helicobacter pylori (HP) plays an important role in gastric cancer occurrence and development. Toll-like receptor 4 (TLR4) and myeloid differential protein-2 (MD-2) are also reported to be involved in gastric cancer cell proliferation and invasion. CXC chemokine receptor 7 (CXCR7), a second receptor for CXCL12, has been detected in multiple types of tumor tissues. Nevertheless, the biological function and regulation of CXCR7 and its relationship with TLR4 and MD-2 in gastric cancer are not completely understood and therefore warrant further study.
METHODS: CXCR7 expression was examined in 150 gastric cancer tissues using immunohistochemistry (IHC). RT-PCR and western blotting were used to detect CXCR7 expression in several gastric cancer cell lines (SGC7901, AGS, MGC-803, MKN-45 and BGC823). shRNAs were designed using a pGPU6/GFP/Neo vector. A CCK-8 assay was used to assess cell proliferation, and transwell assays were performed to assess cell migration. In addition, a gastric cancer xenograft model was generated.
RESULTS: The LPS-TLR4-MD-2 pathway elevates CXCR7 expression in SGC7901 cells, and TLR4/MD-2-mediated increases in CXCR7 levels modulate the proliferation and migration of tumor cells. Knockdown of TLR4 and MD-2 demonstrated that both are essential for LPS-induced CXCR7 expression, which in turn is responsible for LPS-induced SGC7901 cell proliferation and migration. Moreover, higher TLR4, MD-2 and CXCR7 expression was detected in gastric cancer tissues than in paracancerous normal control tissues. The expression levels of TLR4, MD-2 and CXCR7 were closely related to gastric cancer TNM stage and lymph node metastasis. In an animal model, significant differences in CXCR7 expression in tumor masses were observed between the control group and experimental group.
CONCLUSIONS: The results of this study indicate that CXCR7 plays an important role in gastric cancer progression via inflammatory mechanisms, suggesting that CXCR7 could provide a basis for the development and clinical application of a targeted drug for gastric cancer.

PURPOSE: Music has recognized beneficial effects on cancer patients; however, very little is known about the molecular processes which produce these benefits. The aim of this work was to evaluate the effect of music on proliferation and gene expression in gastric cancer cells.
METHODS: AGS gastric cancer cells were exposed to metal and classical music, and subsequently cell proliferation and expression of genes associated with apoptosis and cell-cycle control were evaluated.
RESULTS: Proliferation of AGS cells increased when exposed to metal music, but not when exposed to classical music. Gene expression of caspase-3 and 8 and cyclin B1 increased in response to both musical genres; classical music repressed the expression of p53, and metal music repressed the expression of PUMA.
CONCLUSIONS: This is the first study to demonstrate music as a modulator of gene expression in a cancer cell line. Additional experiments are required to better understand the mechanisms of how different musical genres can induce changes in gene expression.

BACKGROUND/AIM: Merkel cell carcinoma (MCC) is a rare, aggressive, neuroendocrine skin cancer and most MCCs are related to infection with Merkel cell polyomavirus (MCPyV). Notch signaling modulates cell fate in various tissues including the skin during development and homeostasis, and its aberrant activity relates to onset and progression of various malignancies. Therefore, association of NOTCH1/ NOTCH2/NOTCH3/jagged 1 (JAG1) expression with MCPyV status and prognosis in MCC was investigated.
MATERIALS AND METHODS: A total of 19 MCPyV-positive and 19 MCPyV-negative MCC samples from patients were stained immunohistochemically with antibodies against NOTCH1, NOTCH2, NOTCH3, and JAG1 and analyzed.
RESULTS: Expression of NOTCH1 and NOTCH2 was not associated with MCPyV status or prognosis. However, higher JAG1 expression was found in MCPyV-negative than in MCPyV-positive MCC (p<0.001), and NOTCH3 expression was higher in MCPyV-positive MCC (p=0.062). Kaplan-Meier and multivariate analyses showed that patients with MCC with higher NOTCH3 expression had better overall survival than otherwise (p=0.001 and p=0.033, respectively).
CONCLUSION: Expression of NOTCH3, as a tumor suppressor, is an independent predictor of MCC outcome.

The epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) formation are two paramount processes driving tumor progression, therapy resistance, and cancer metastasis. Recent experiments show that cells with varying EMT and CSC phenotypes are spatially segregated in the primary tumor. The underlying mechanisms generating such spatiotemporal dynamics in the tumor microenvironment, however, remain largely unexplored. Here, we show through a mechanism-based dynamical model that the diffusion of EMT-inducing signals such as TGF-β, together with noncell autonomous control of EMT and CSC decision making via the Notch signaling pathway, can explain experimentally observed disparate localization of subsets of CSCs with varying EMT phenotypes in the tumor. Our simulations show that the more mesenchymal CSCs lie at the invasive edge, while the hybrid epithelial/mesenchymal (E/M) CSCs reside in the tumor interior. Further, motivated by the role of Notch-Jagged signaling in mediating EMT and stemness, we investigated the microenvironmental factors that promote Notch-Jagged signaling. We show that many inflammatory cytokines such as IL-6 that can promote Notch-Jagged signaling can (

BACKGROUND/AIMS: Jagged1 is the ligands of the Notch signaling and has been shown to promote glioma-initiating cells (GICs) in glioblastoma. The role of Jagged1 in GICs invasion and underlying molecular mechanisms remain unclear.
METHODS: Survival data from R2 genomics analysis, the Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA) and visualization platform database were used to evaluate the effects of Jagged1 on overall patient survival. we investigated Jagged1 induced the GICs cells' invasion by matrix degradation assays and Transwell cell invasion assays in vitro, then we further explored the underlying molecular mechanisms using Co-immunoprecipitation (co-IP) analysis.
RESULTS: High expression of Jagged1 in human glioma was associated with poor survival. Clinical data analysis showed that the Jagged1 was positively correlated with NF-κB(p65). Jagged1-induced invasion of GICs cells through activation of NF-κB(p65) pathway. In vivo, knockdown of Jagged1 could suppress the tumorigenicity of GICs cells through NF-κB(p65) signaling.
CONCLUSION: Insights gained from these findings suggest that Jagged1 plays an important oncogenic role in GICs malignancy by activation of NF-κB(p65) signaling, and Jagged1 could be employed as an effective therapeutic target for GICs.

Gastric cancer is one of the most common malignant tumors worldwide and has the second highest incidence and mortality rate among malignant tumors in China. Prostate-derived Ets factor (PDEF) is a member of the Ets family of transcription factors. Although PDEF plays an important role in tumorigenesis, its biological function in gastric cancer is still unclear. Here, we evaluated PDEF expression in 30 cases of human gastric carcinoma and the corresponding peritumoral tissues, using immunohistochemistry and immunofluorescence. Significantly higher levels of PDEF were detected in tumors compared to peritumoral tissues. We then investigated PDEF expression in the gastric cancer cell lines SGC and AGS and the normal gastric epithelial cell line GES; The CRISPR/Cas9 genome-editing system was used to knockout PDEF in AGS cells as a model for gastric cancer. Cell proliferation, apoptosis, migration, and invasion of PDEF-knockout AGS cells were evaluated using CCK-8, flow cytometry, scratch wound, and transwell assays, respectively. The results illustrated that PDEF-knockout inhibited AGS cell proliferation, migration, and invasion. Taken together, the results imply that PDEF plays important roles in the proliferation, migration, and invasion of AGS cells and may serve as a new treatment target in gastric cancer.

BACKGROUND: Previous studies demonstrated that miR-539 play an important role in the carcinogenesis of some cancers. The aim of the present study was to determine the role of miR-539 in the pathogenesis of Wilms' Tumor (WT).
METHODS: The expression level of miR-539 was measured by qRT-PCR in 42 WT tissues and SK-NEP-1 cell line. Protein expression of genes (E-cadherin, N-cadherin, Vimentin, Notch 1, Notch 3 and JAG1) was assessed by Western blot. The function of miR-539 was investigated in SK-NEP-1 cells by MTT and Transwell assays. The relationship between miR-539 and JAG1 was verified by a dual luciferase assay in SK-NEP-1 cells.
RESULTS: The expression level of miR-539 was significantly decreased in WT tissues. Downregulation of miR-539 was closely related to NWTS-5 stage, lymph node metastasis and histological type of WT patients. Furthermore, low miR-539 expression was associated with a shorter overall survival rate in WT patients. In vitro, overexpression of miR-539 suppressed proliferation, migration and invasion of SK-NEP-1 cells. In addition, JAG1 was a direct target of miR-539. MiR-539 inhibited the development of WT by inhibiting JAG1-Notch1/3 expressing and blocking EMT.
CONCLUSION: MiR-539 inhibited the progression of WT through downregulation of JAG1 and Notch1/3.

AIMS: Ruthenium-based compounds exhibit critical biochemical properties making them suitable for diverse pharmacological applications. The aim of this work was to study the anticancer effects of three ruthenium complexes on a human gastric cancer cell line.
MAIN METHODS: We synthetized three [Ru(η
KEY FINDINGS: Compound 3 exhibited the highest cytotoxicity (IC
SIGNIFICANCE: Our data suggests that compound 3 may be an interesting anticancer molecule for the treatment of gastric cancer.

BACKGROUND & AIMS: Gastritis is associated with development of stomach cancer, but little is known about changes in microRNA expression patterns during gastric inflammation. Specific changes in gene expression in epithelial cells are difficult to monitor because of the heterogeneity of the tissue. We investigated epithelial cell-specific changes in microRNA expression during gastric inflammation and gastritis-associated carcinogenesis in mice.
METHODS: We used laser microdissection to enrich epithelial cells from K19-C2mE transgenic mice, which spontaneously develop gastritis-associated hyperplasia, and Gan mice, which express activated prostaglandin E2 and Wnt in the gastric mucosa and develop gastric tumors. We measured expression of epithelial cell-enriched microRNAs and used bioinformatics analyses to integrate data from different systems to identify inflammation-associated microRNAs. We validated our findings in gastric tissues from mice and evaluated protein functions in gastric cell lines (SNU-719, SNU-601, SNU-638, AGS, and GIF-14) and knockout mice. Organoids were cultured from gastric corpus tissues of wild-type and miR-135b-knockout C57BL/6 mice. We measured levels of microRNAs in pairs of gastric tumors and nontumor mucosa from 28 patients in Japan.
RESULTS: We found microRNA 135b (miR-135B) to be the most overexpressed microRNA in gastric tissues from K19-C2mE and Gan mice: levels increased during the early stages of gastritis-associated carcinogenesis. Levels of miR-135B were also increased in gastric tumor tissues from gp130
CONCLUSIONS: We found expression of miR-135B to be up-regulated by interleukin L1 signaling in gastric cancer cells and organoids. miR-135B promotes invasiveness and stem-cell features of gastric cancer cells in culture by reducing FOXN3 and RECK messenger RNAs. Levels of these messenger RNA targets, which encode tumor suppressor, are reduced in human gastric tumors.

BACKGROUND & AIMS: microRNAs (miRNAs) are small noncoding RNAs that bind to the 3' untranslated regions of mRNAs to promote their degradation or block their translation. Mice with disruption of the trefoil factor 1 gene (Tff1) develop gastric neoplasms. We studied these mice to identify conserved miRNA networks involved in gastric carcinogenesis.
METHODS: We performed next-generation miRNA sequencing analysis of normal gastric tissues (based on histology) from patients without evidence of gastric neoplasm (n = 64) and from TFF1-knockout mice (n = 22). We validated our findings using 270 normal gastric tissues (including 61 samples from patients without evidence of neoplastic lesions) and 234 gastric tumor tissues from 3 separate cohorts of patients and from mice. We performed molecular and functional assays using cell lines (MKN28, MKN45, STKM2, and AGS cells), gastric organoids, and mice with xenograft tumors.
RESULTS: We identified 117 miRNAs that were significantly deregulated in mouse and human gastric tumor tissues compared with nontumor tissues. We validated changes in levels of 6 miRNAs by quantitative real-time polymerase chain reaction analyses of neoplastic gastric tissues from mice (n = 39) and 3 independent patient cohorts (n = 332 patients total). We found levels of MIR135B-5p, MIR196B-5p, and MIR92A-5p to be increased in tumor tissues, whereas levels of MIR143-3p, MIR204-5p, and MIR133-3p were decreased in tumor tissues. Levels of MIR143-3p were reduced not only in gastric cancer tissues but also in normal tissues adjacent to tumors in humans and low-grade dysplasia in mice. Transgenic expression of MIR143-3p in gastric cancer cell lines reduced their proliferation and restored their sensitivity to cisplatin. AGS cells with stable transgenic expression of MIR143-3p grew more slowly as xenograft tumors in mice than control AGS cells; tumor growth from AGS cells that expressed MIR143-3p, but not control cells, was sensitive to cisplatin. We identified and validated bromodomain containing 2 (BRD2) as a direct target of MIR143-3p; increased levels of BRD2 in gastric tumors was associated with shorter survival times for patients.
CONCLUSIONS: In an analysis of miRNA profiles of gastric tumors from mice and human patients, we identified a conserved signature associated with the early stages of gastric tumorigenesis. Strategies to restore MIR143-3p or inhibit BRD2 might be developed for treatment of gastric cancer.

Fibroblast growth factor receptor 1 (FGFR1) has been reported in gastric cancer to be a prognostic factor. However, miR-497-targeted FGFR1 has not been explored in the carcinogenesis of gastric cancer. The present study intended to revalidate the prognostic significance of FGFR1 in patients with gastric cancer, and the mechanism of miR-497-regulated FGFR1 was investigated in gastric cancer cell proliferation and apoptosis. The messenger RNA (mRNA) and protein levels were assayed by RT-qPCR and western blotting, respectively. The targeted genes were predicted by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. Cell proliferation was analyzed by CCK-8 assay. Annexin V-FITC/PI staining was used to evaluate the apoptosis in AGS and SGC-7901 cells. FGFR1 was frequently up-regulated in gastric cancer tissues and associated with poor overall survival in patients with gastric cancer. Interestingly, FGFR1 loss-of-function resulted in a significant growth inhibition and apoptosis in AGS and SGC-7901 cells. In addition, we found that miR-497 was inhibited in gastric cancer tissues and cell lines, while overexpression of miR-497 could suppress proliferation and induce apoptosis in AGS and SGC-7901 cells. Importantly, bioinformatics analysis and experimental data suggested that FGFR1 was a direct target of miR-497, which could inhibit FGFR1 expression when transfected with miR-497 mimics. Furthermore, we found that overexpression of FGFR1 reversed the growth inhibition and apoptosis of miR-497 mimics in AGS and SGC-7901 cells. These findings suggested that overexpression of miR-497 inhibited proliferation and induced apoptosis in gastric cancer through the suppression of FGFR1.

The role of perfluorodecanoic acid (PFDA) in gastric carcinogenesis and its mechanism remains unknown. Our previous research revealed that PFDA regulated the growth of human gastric cells. However, its core molecules and basic mechanisms are still not clear. In the present study, cDNA microarrays were used to determine mRNA changes in AGS cells after treatment with PFDA. DAVID analysis of the genes with >2‑fold increased expression in microarray data revealed five genes which were involved in cancer pathways. The most upregulated gene was cIAP2, whose upregulation in AGS was confirmed by western blot analysis and quantitative PCR (qPCR) analyses. In order to investigate the role of cIAP2 in cell proliferation, cIAP2 siRNA was employed to regulate cIAP2 expression following PFDA treatment. The results revealed that the growth rate of cIAP2‑knockdown cells was reduced by about 50% compared to the control. Given that our previous flow cytometric assays revealed no significant change (3.7 vs. 6.4%) in the percentage of apoptotic cells when PFDA was added to the medium and cIAP2 expression was upregulated, we next applied flow cytometry to assess whether cIAP2 would lead to cell cycle variations. The research data revealed that the proportion of cells in the G1, S and G2 phases was not significantly altered with the decrease of cIAP2 expression. Finally, the role of cIAP2 in AGS cell senescence was investigated, and the results indicated that cell senescence was significantly increased in the cIAP2 siRNA group in comparison to the control siRNA group. Since p53 has been identified as a tumor suppressor and its molecular alterations are common in different human tumors, we investigated the relationship of p53 with cIAP2. The experimental results demonstrated that cIAP2 regulated the expression of p53 and thus was likely to be a potential mechanism for PFDA‑induced growth promotion. Overall, the results revealed that PFDA may suppress cellular senescence induced by p53 through the regulation of cIAP2 protein expression.

In the present study, proteins differentially expressed between gastric cancer tissue and para‑tumoral normal gastric tissues were screened, and the function of the highly expressed protein C1QTNF6 in gastric carcinoma was investigated. The differential expression of mRNAs extracted from the tumor and adjacent tissues was analyzed using GeneChip assay. An AGS si‑C1QTNF6 cell line was constructed using shRNA‑C1QTNF6 lentivirus. The cell invasion and migration ability of C1QTNF6‑knockdown cells were determined by Transwell chamber migration and wound healing assays, respectively. The effects of C1QTNF6 on AGS cell cycle distribution and apoptosis were detected using a FACScan flow cytometer. The results demonstrated that the expression of 109 genes was increased and the expression of 129 was decreased in tumor tissues. Among these genes, the C1QTNF6 gene was highly expressed in tumor tissues and the AGS7901 cell line. C1QTNF6‑knockdown decreased the cell growth, and the proliferative and migration ability, as well as increasing the apoptosis of gastric carcinoma cells. In addition, the number of AGS cells in the G2/M phase was significantly increased after 5 days of C1QTNF6‑shRNA lentivirus infection. The results of the present study indicated that C1QTNF6 serves an important role in the development of gastric carcinoma. C1QTNF6 is involved in promoting the proliferation and migration, and in reducing the apoptosis of gastric carcinoma cells. These results provided a potential therapeutic target for the treatment of gastric carcinoma.

The present study investigated the effects of Colchicine on gastric carcinoma (GC) cells and explored its possible mechanisms underlying such effects. The results of MTT and colony formation assays showed that Colchicine (2, 5, and 10 ng/ml) markedly inhibited the proliferation of AGS and NCI-N87 cells in a dose-dependent manner. It also led to a reduction in cell migration in both GC cells as determined by Transwell migration assay. Mover, data form Hoechst 33342 staining and flow cytometry assay indicated that Colchicine (2, 5, and 10 ng/ml) promoted the apoptosis of NCI-N87 cells. In addition, the release of cytochrome

BACKGROUND: Previous studies indicated that miR-218 was deregulated in gastric cancer patients and correlated with tumor invasion and prognosis. The aim of this study was to clarify the effect of miR-218 on the malignant behavior of gastric cancer and its role in regulating Bmi-1/Akt signaling pathway.
MATERIALS AND METHODS: We used miR-218 mimic to transfect gastric cancer cell lines AGS and SGC-7901, and the overexpression efficiency was validated using qRT-PCR assay. MTT assay and Transwell chamber system were performed to detect the effect of miR-218 on cell proliferation, invasion and migration on gastric cancer. Western blot and qRT-PCR assay was used to test the role of miR-218 in regulating Bmi-1/Akt signaling pathway.
RESULTS: As shown in our research, ectopic expression of miR-218 in gastric cancer cells inhibits the proliferation, invasion and migration of gastric cancer cells. In addition, miR-218 re-expression inhibits the expression of Bmi-1 and its downstream target p-Akt
CONCLUSIONS: miR-218 inhibits the proliferation, invasion and migration of gastric cancer cells through modulating EMT process and the expression of MMPs via Bmi-1/Akt signaling pathway.