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• 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]