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BACKGROUND: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a common malignant tumor associated with EBV infection. Insulin-like growth factor 2 (IGF2) is an imprinted gene and a key protein that regulates growth, especially during normal fetal development. Loss of imprinting (LOI), is a common epigenetic anomaly in a variety of human cancers. However, the promoter methylation, imprinting status and function of IGF2 gene in GC are unclear. OBJECTIVE: To explore the role of IGF2 in the occurrence and development of gastric cancer. METHODS: The biological function of IGF2 in gastric cancer was investigated by Transwell, wound healing, CCK-8 and flow cytometry assays. IGF2 imprinting status and gene promoter methylation in gastric cancer tissues were detected by PCR-RFLP and BGS. RESULTS: The results showed that the expression of IGF2 was higher in GC tissues than adjacent tissues. IGF2 gene promoter methylation and LOI were significantly higher in EBVaGC tissues than in EBV-negative gastric cancer (EBVnGC) tissues. The high expression of IGF2 in gastric cancer can promote the migration and proliferation of gastric cancer cells. CONCLUSION: Our data suggest that IGF2 is involved in the occurrence and development of gastric cancer. Targeting IGF2 may be a potential therapeutic target for gastric cancer. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) is an important DNA virus which establishes latent infection in human malignancies. Expression of EBV-encoded genes in the associated tumors is strongly modulated by promoter CpG methylation of EBV genome. This study aimed to explore the methylation status of the promoters of EBV BamHI-A rightward frame 1 (BARF1) and BamHI-H rightward open reading frame 1 (BHRF1) and their influence on transcriptional expression, to further understand the roles of BARF1 and BHRF1 in the occurrence of EBV-associated cancer. We evaluated the methylation status of BARF1 and BHRF1 promoters in 43 EBV-associated gastric carcinoma (EBVaGC) tissues and EBV-positive cell lines. Their expressions were evaluated by real-time quantitative PCR. We found that the promoters of BARF1 and BHRF1 were methylated by varying degrees in different EBV-positive cell lines and were almost hypermethylated in all EBVaGC tissues. The methylation status of BARF1 and BHRF1 promoters were significantly reduced by 5-Aza-CdR along with the increasing gene expressions. Hypermethylation of Ap and Hp mediates the frequent silencing of BARF1 and BHRF1 in EBV-associated tumors, which could be reactivated by a demethylation agent, suggesting that promoter demethylation and activation is important for BARF1 and BHRF1 transcription and their further action. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder caused by the interaction of environmental factors and multiple genes. The genetic background of T2DM is complex and remains to be fully elucidated. MicroRNAs (miRNAs) are negative regulators of gene expression and several miRNAs are associated with the development of T2DM. However, the expression and biological function of miRNA-9-3p in lipid metabolism of patients with T2DM remain to be fully elucidated. The predominant aim of the present study was to examine the effect of miRNA-9-3p on lipid accumulation in HepG2 cells. To investigate this, an MTT assay was used to determine cell proliferation, and the effects of miRNA-9-3p on triglycerides (TG) and total cholesterol (TC) in the HepG2 cells were also examined. Reverse transcription-quantitative polymerase chain reaction and western blot analyses were used to measure the expression levels of SIRT1 at the gene and protein levels, respectively. The date revealed that downregulation of miRNA-9-3p inhibited the proliferation of HepG2 cells, and significantly reduced the accumulation of lipids, and decreased TG and TC content. In addition, the present study demonstrated that inhibition of miRNA-9-3p increased the protein expression of sirtuin type 1 (SIRT1), but had no effects on the gene expression of SIRT1. Therefore, these findings demonstrated that the inhibition of miRNA-9-3p reduced the proliferation of HepG2 cells and lipid accumulation by upregulating the expression of SIRT1, indicating its potential as a therapeutic target. [ABSTRACT FROM AUTHOR]

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Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) are the most highly expressed transcripts in all EBV-associated tumors and are involved in both lymphoid and epithelioid carcinogenesis. Our previous study on Chinese isolates from non-endemic area of nasopharyngeal carcinoma (NPC) identified new EBER variants (EB-8m and EB-10m) which were less common but relatively more frequent in NPC cases than healthy donors. In the present study, we determined the EBER variants in NPC cases and healthy donors from endemic and non-endemic areas of NPC within China and compared the EBER variants, in relation to the genotypes at BamHI F region (prototype F and f variant), between population groups and between two areas. According to the phylogenetic tree, four EBER variants (EB-6m, EB-8m, EB-10m and B95-8) were identified. EB-6m was dominant in all population groups except for endemic NPC group, in which EB-8m was dominant. EB-8m was more common in endemic NPC cases (82.0%, 41/50) than non-endemic NPC cases (33.7%, 32/95) (p<0.0001), and it was also more frequent in healthy donors from endemic area (32.4%, 24/74) than healthy donors from non-endemic area (1.1%, 1/92) (p<0.0001). More importantly, the EB-8m was more prevalent in NPC cases than healthy donors in both areas (p<0.0001). The f variant, which has been suggested to associate with endemic NPC, demonstrated preferential linkage with EB-8m in endemic isolates, however, the EB-8m variant seemed to be more specific to NPC isolates than f variant. These results reveal high prevalence of EBER EB-8m variant in endemic NPC cases, suggesting an association between NPC development and EBV isolates carrying EB-8m variant. Our finding identified a small healthy population group that shares the same viral strain which predominates in NPC cases. It could be interesting to carry extensive cohort studies following these individuals to evaluate the risk to develop NPC. [ABSTRACT FROM AUTHOR]

The brown planthopper (BPH) Nilaparvata lugens is an economically important pest on rice plants. In this study, the higher population density and yellow-ripe stage of rice plants were used to construct adverse survival conditions (ASC) against BPH nymphs. Simultaneously, the low population density and tillering stage of rice plants were used to establish a suitable survival condition (SSC) as a control. Solexa/Illumina sequencing was used to identify genes of BPH nymphs responding to ASC. Significantly longer duration development of BPH nymphs and significantly lower brachypterous ratio of BPH adults were observed by ASC compared with SSC. A total of 2 544 differentially expressed genes (DEGs) were obtained and analyzed by BLASTx, Gene Ontology and KEGG Orthology. Gene ontology analysis revealed that the DEGs were mainly involved in categories of cell, cell part, cellular process, binding, catalytic, organelle and metabolic processes. 1 138 DEGs having enzyme commission numbers were assigned to different metabolic pathways. The largest clusters were neurodegenerative diseases (137, 12.0%), followed by carbohydrate metabolism (113, 9.9%), amino acid metabolism (94, 8.3%), nucleotide metabolism (76, 6.7%), energy metabolism (64, 5.6%), translation (60, 5.3%), lipid metabolism (58, 5.1%), and folding, sorting and degradation (52, 4.6%). Expressing profile of 11 DEGs during eight nymphal developmental stages of BPH were analyzed by quantitative real-time polymerase chain reaction. The 11 genes exhibited differential expression between ASC and SSC during at least one developmental stage. The DEGs identified in this study provide molecular proof of how BPH reconfigures its gene expression profile to adapt to overcrowding and low-quality hosts. [ABSTRACT FROM AUTHOR]

Inhibitor of DNA binding differentiation 3 (Id3), a member of the Id helix-loop-helix protein family, plays important roles in cell differentiation, cell cycle control, and apoptosis. In the present study, the human Id3 ( hId3) gene was amplified by polymerase chain reaction and inserted into prokaryotic expression vector pET32a(+). The recombinant plasmid pET32a/ hId3 was transformed into Escherichia coli BL21 (DE3). The histidine-Tag-fused protein was expressed by induction of 1 mM isopropylthio-β- d-galactoside and purified by Ni2+-nitrilotriacetic acid-agarose column chromatography. The purified hId3 protein was used to generate rabbit polyclonal antisera that recognize recombinant hId3 (rhId3). The antibody was purified by polypeptide affinity chromatography and used for analysis of Id3 subcellular localization in several kinds of tumor cells by indirect immunofluoresence assay. A large quantity of purified rhId3 protein and polyclonal anti-hId3 antibodies would be useful reagents for the further study of biological functions of hId3. [ABSTRACT FROM AUTHOR]

• EBV can upregulate the PI3K/AKT pathway through its encoded EBER1 and LMP2A, thereby promoting the expression of YAP1 in EBVaGC cells. • YAP1 enhances the proliferation, migration, autophagy, S-phase accumulation, and anti-apoptotic ability of EBVaGC cells, which may play carcinogenic role in EBVaGC progression. • YAP1 also enhances EBV replication, and TPA and NaB induced EBV lytic reactivation, forming a bidirectional regulatory mechanism with EBV, further promoting the development of EBVaGC. This study aims to explore the role and regulatory mechanism of Yes-associated protein 1 (YAP1) in the development of Epstein-Barr virus-associated gastric cancer (EBVaGC). Here we showed that EBV can upregulate the expression and activity of YAP1 protein through its encoded latent products EBV-encoded small RNA 1 (EBER1) and latent membrane protein 2A (LMP2A), enhancing the malignant characteristics of EBVaGC cells. In addition, we also showed that overexpression of YAP1 induced the expression of EBV encoding latent and lytic phase genes and proteins in the epithelial cell line AGS-EBV infected with EBV, and increased the copy number of the EBV genome, while loss of YAP1 expression reduced the aforementioned indicators. Moreover, we found that YAP1 enhanced EBV lytic reactivation induced by two known activators, 12-O-tetradecanoylhorbol-13-acetate (TPA) and sodium butyrate (NaB). These results indicated a bidirectional regulatory mechanism between EBV and YAP1 proteins, providing new experimental evidence for further understanding the regulation of EBV infection patterns and carcinogenic mechanisms in gastric cancer. [ABSTRACT FROM AUTHOR]

Abstract: Angiotensin II is a powerful mediator to induce cardiac remodeling and fibrosis. Transforming growth factor-β1 (TGF-β1) and extracellular signal-regulated kinase (ERK) have been implicated in the angiotensin II-induced cardiac fibrosis. However, the signaling pathways for this angiotensin II effect and the interaction between ERK and the TGF-β1 signaling in this effect have not been well-illustrated. Cardiac fibroblasts were prepared from the ventricles of adult male Sprague–Dawley rats. They were treated with 1 µM angiotensin II in the presence or absence of losartan (angiotensin II AT1 receptor antagonist), PD123319 (angiotensin II AT2 receptor antagonist), an anti-TGF-β1 antibody or PD98059 (ERK inhibitor). The cells were collected for Western blotting and reverse transcription-polymerase chain reaction. Angiotensin II caused a significant increase of the expression of TGF-β1, ERK1, phosphorylated-Smad2/3, Smad4 and collagen I. This increase was attenuated by losartan but was not affected by PD123319. An anti-TGF-β1 antibody and PD98059 diminished angiotensin II-induced Smad2/3 phosphorylation and the expression of Smad7 and collagen I. Our results suggest that angiotensin II induces collagen I expression through angiotensin II AT1 receptor-TGF-β1-Smads signaling pathway in cardiac fibroblasts. ERK, by regulating Smads signaling, also participated in the angiotensin II-induced collagen I expression. [Copyright &y& Elsevier]

Epstein-Barr virus (EBV) infection is closely related to gastric carcinoma (GC). In this study, we identified a set of DEGs (different expression genes) between EBVaGC (EBV-associated gastric carcinoma) and EBVnGC (EBV-negative gastric carcinoma) through multiple bioinformatics analysis using the data from GEO (Gene Expression Omnibus) dataset GSE51575, and identified ten hub genes (CXCL10, C3, CXCL9, CXCL11, SST, ICAM1, CHRM2, NPY, GBP5 and GBP1). Therefore, we performed relevant survival analysis and immune infiltration analysis, then verified the mRNA expression in GC cell lines and TCGA database. CXCL11 was finally selected to be a potential biomarker for a better prognosis and tumor infiltrating. This may provide a new view about immune therapy for EBVaGC. [ABSTRACT FROM AUTHOR]