Transcriptomic analysis of pathway activation after decitabine treatment in EBV+ vs EBV- gastric cancer [RNA-Seq]
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE309938 | GEO | 2025/11/14
REPOSITORIES: GEO
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Project description:Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a distinct entity that has conspicuously tumor microenvironment compared with EBV-negative gastric carcinoma. However, the exact role of EBV in gastric carcinogenesis remains elusive. In the present study, we found that EBV upregulated CXCL8 expression, and CXCL8 significantly promoted vasculogenic mimicry (VM) formation of gastric carcinoma cells. In accordance with these observations, CXCL8 increased cell proliferation and migration of AGS and BGC823 cells, respectively. In addition, activation of NF-κB signaling was involved in VM formation induced by CXCL8, which was blocked by NF-κB inhibitor BAY 11-7082. Furthermore, EBV encoded lncRNA RPMS1 activated the NF-κB signaling cascade, which is responsible for EBV-induced VM formation. Both xenografts and clinical samples of EBVaGC exhibit VM histologically, which are correlated with CXCL8 over-expression. Finally, CXCL8 is positively correlated with overall survival in gastric carcinoma patients. In conclusion, EBV-upregulated CXCL8 expression promotes VM formation in gastric carcinoma via NF-κB signaling and CXCL8 may serve as a novel anti-tumor target for EBVaGC.
2021-10-14 | GSE185627 | GEO
Project description:[Aim] EBVaGC accounts for about 10% of gastric cancer and has a better prognosis than EBVnGC, but its molecular mechanism is still unclear. We investigated the role of EBV-miR-BART1-3p in the occurrence and development of EBVaGC by applying bioinformatics methods, high-throughput sequencing, in vitro experiments, target gene screening and verification, differential gene protein interaction network and gene regulatory network construction. [Materials and Methods] The data set GSE51575 was normalized, and the outlier samples were deleted. Finally, gene expression profiles of 11 EBVaGC and 14 EBVnGC tumor tissues and non-tumor control tissues were obtained. Differential gene function analysis was performed, and molecular regulatory network was constructed. The mRNA expression levels of SNU-719 (EBV-positive gastric cancer cell line), AGS, AGS-NC (EBV-negative gastric cancer cell line) and AGS-OE (lentivirus-transfected miR-BART1-3p overexpression cell line) were detected by high-throughput next-generation sequencing technology, and differential gene expression characteristics were analyzed. To investigate the effect of miR-BART1-3p overexpression on mRNA expression level of gastric cancer cells and construct the protein interaction network of differential genes and the regulatory network of miR-BART1-3p gene. DIANA-MR micro-T, miRnada, miRDB, TarBase v.8, and ViRBase online databases were used to predict the target genes of miR-BART1-3p and GO enrichment analysis of target gene function was performed. Real-time fluorescence quantitative PCR was used to detect the expression levels of miR-BART1-3p and target genes in SNU719, AGS-OE and AGS gastric cancer cells. The effects of overexpression of EBV-miR-BART1-3p on proliferation, apoptosis, invasion, and migration of gastric cancer cells were investigated by CCK-8, cell cloning, cell scratch and Transwell. [Results] By analyzing the gene expression profile of the GSE51575 dataset, we found that EBVaGC up-regulated the expression of immune cell membrane protein receptors and chemokine family, and was involved in inducing tumor immunity, suggesting a better prognosis. EBVnGC significantly up-regulated the expression of AURK, BUB1B, CCNA2 and CDC20, suggesting the risk of malignant progression and recurrence. High-throughput next-generation sequencing of SNU719 and AGS to detect differences in gene expression revealed that EBVaGC cells (SNU719) up-regulated the expression of genes that inhibit malignant progression as well as potential tumor immunotherapy targets. These results are consistent with those found in the GSE51575 dataset. Fifteen miR-BART1-3p target genes, including FAM168A, TET3, HBP1, ZBTB5, ATXN7L3, KMT5C, SPARC and BMF, were predicted and screened by online tools. After the overexpression of miR-BART1-3p in AGC(EBVnGC) cells, the proliferation, migration, and invasion ability were significantly inhibited, and the signaling pathway promoting tumor progression was also limited in activation. [Conclusions] The overexpression of miR-BART1-3p may inhibit the proliferation and invasion and migration of gastric cancer cells by inhibiting the activation of STAT3/ pSTAT3 and PI3K/AKT signaling pathways and may become a target for the treatment of EBVaGC, which is worthy of further study.
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Project description:We investigate the expression of miRNA in exosome of EBV-positive gastric carcinoma cells. The exosomes of EBV-positive and negative gastric carcinoma cells were separated by ultracentrifugation, the morphology of exosomes was identified by transmission electron microscopy, the exosome size was analyzed by Nanosight, and the expression of exosome membrane protein CD63 and CD81 was detected by western blot. High-throughput sequencing was used to detect miRNA expression profiles in gastric cancer cell lines and their exosomes. Under the ultra-microscopic electron microscope, the exosomes are seen as a typical translucent cup-like structure or a flat spherical structure. The nanoparticle tracking analyzer (Nanosight) showed that the exosomes were between 30 and 150 nm in diameter. Western blot(WB) assays showed that exosomes secreted by EBVaGC and EBVnGC cells expressed specific exosome membrane-associated proteins CD63 and CD81. High-throughput sequencing revealed that EBVaGC(SNU-719) and EBVnGC(AGS) and their secreted exosomes were highly expressed with certain human miRNAs, among which AGS-exo was highly expressed with hsa-miR-23b-3p, hsa-miR-320a-3p, and hsa-miR-4521. SNU-719-exo was highly expressed as hsa-miR-21-5p, hsa-miR-148a-3p and hsa-miR-7-5p. Nearly all EBV-related miRNAs (EBV-miRNA) were expressed in SNU-719 cells and their exosomes, among which EBV-miR-BART1-5p, EBV-miR-BART17-3p and EBV-miR-BART18-5p were the highest in SNU-719 cells, EBV-miR-BART1-5p, EBV-miR-BART18-5p and EBV-miR-BART17-3p were the highest in SNU-719-exo.
2022-03-14 | GSE198354 | GEO
Project description:Gastric cancer is one of the most common cancers worldwide. Epstein-Barr virus-associated gastric cancer accounts for approximately 10% of all gastric cancers. EBV expresses its own proteins and miRNAs (BART miRNAs) and regulates host gene expression. In this study, we examined the effect of EBV infection on host mRNA expression. Differential gene expression was analyzed between EBV-negative human gastric cancer cell line AGS and EBV-positive human gastric cancer cell line AGS-EBV.
2019-10-14 | GSE135644 | GEO
Project description:EBV microRNAs, especially rightward transcript (BART) microRNAs play key roles in the tumor growth of EBVaGC. However, the effects of EBV-miR-BART19-3p in EBVaGC remain largely unknown. Here, we report that EBV-miR-BART19-3p is highly expressed in EBVaGC and promoted the proliferation of EBV-associated gastric cancer cells in vitro and accelerate xenograft tumor growth in vivo. Molecularly, EBV-miR-BART19-3p directly targets the growth arrest and DNA damage-inducing protein Beta mRNA (GADD45B) and downregulates its protein expression, which consequently reduce cell cycle G2/M phase arrest. Reconstitution of GADD45B can rescue the proliferation phenotype caused by EBV-miR-BART19-3p in EBVaGC cells, highlighting the role of GADD45B in EBV-miR-BART-driven Gastric cancer. Our study indicated Epstein-Barr Virus MicroRNA BART19-3p played an oncogenic role by a novel mechanism of inhibiting GADD45B in EBVaGC, which provides new insights and might be a potential therapeutic strategy for EBVaGC patients.
2025-07-22 | GSE302909 | GEO
Project description:Gastric cancer is one of the most common cancers worldwide. Epstein-barr virus-associated gastric cancer accounts for about 10% of all gastric cancers. EBV itself expresses a variety of proteins and regulates the expression of host genes. In this study, we examined the knockdown of BC200 and eIF4A3 in AGS-EBV, respectively, and analyzed its effect on host mRNA expression.
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Project description:In EBV-associated tumors, such as gastric cancer (GC) and Burkitt’s lymphoma (BL), a high proportion of microRNAs are virally encoded. To explore the targets of both viral and host microRNAs, we performed Crosslinking, Ligation, and Sequencing of Hybrids (CLASH). With this approach, we were able to quantify each Argonaute-bound microRNA-mRNA interaction in a GC (SNU719), and BL (Akata) cell line.
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Project description:In this study, we established a successive xenograft model to enrich Epstein-Barr virus-associated gastric carcinoma (EBVaGC) cancer stem cells (CSCs) through long-term treatment of EBVaGC cell line SNU719 with 5-Fluorouraci (5-Fu) in mice vivo passage. Simply, NOD/SCID mice injected in the subcutaneous with SNU719 were treated with 5-Fu weekly until xenografts reached 1.5 cm diameter and the mice were euthanizedand single-cell suspensions were obtainedby collagenasedigestion. Then the purified cells were passaged in 5-Fu-treated NOD/SCID mice as above. After four successive generations,we obtained theSNU-4th cells from the fourth passage xenografts treated with 5-Fu. Compared with parental SNU719 cells, SNU-4th cells possessed the stemness characters. Increasing evidence have proved that circular RNA (circRNA) play an important role in maintaining the tumor phenotype. So, we compared circRNAs expression between the fourth passage xenografts treated with 5-Fu and PBS by RNA-sequencing, hoping to find out which circRNAs were involved in the stemness regulation of EBVaGC. we established a highly malignant EBVaGC cell line SNU-4th through long-term treatment of EBVaGC cell line SNU719 with 5-Fluorouraci in vivo passage, then we compared circRNAs expression between the fourth passage xenografts treated with 5-Fu and PBS by RNA-sequencing
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Project description:Reactive oxygen species (ROS) mediated oxidative stress plays an increasingly extensive role in tumorigenesis. Oxidative stress is also an important mechanism for host cells to resist infection by pathogenic microorganisms. Viruses have a similar defense mechanism. Studies have shown that ROS levels are elevated during in vitro and in vivo EBV infection. In nasopharyngeal carcinoma, EBV latent membrane protein LMP1 "REDOX" nasopharyngeal carcinoma cells by up-regulating NRF2 and NOX2, acquiring new REDOX homeostasis to tolerate higher levels of ROS. In gastric cancer, EBV upregulates NOX2 by down-regulating miR34a via EBNA1, thereby enhancing the antioxidant capacity of host cells. In addition, oxidative stress is involved in the lytic reactivation of EBV, but the specific mechanism is not clear. GPX4 is an important ROS scavenger that plays a role in maintaining cellular REDOX homeostasis. Our study showed that GPX4 is relatively highly expressed in EBV-positive gastric cancer cell lines, which can promote tumor proliferation and migration, and we found that GPX4 helps maintain latent infection of EBV in gastric cancer. In order to further explore the specific mechanism, we performed transcriptome sequencing analysis after knocking down GPX4 expression in AGS-EBV cells.
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