Epstein-Barr Virus miR-BART1-3p Regulates the miR-17-92 Cluster by Targeting E2F3.

Epstein-Barr virus (EBV) is associated with several tumors and generates BamHI A rightward transcript (BART) microRNAs (miRNAs) from BART transcript introns. These BART miRNAs are expressed at higher levels in EBV-associated epithelial malignancies than in EBV-infected B lymphomas. To test the effects of EBV miRNA on the cell cycle and cell growth, we transfected miR-BART1-3p, a highly expressed EBV-associated miRNA, into gastric carcinoma cells. We found that miR-BART1-3p induced G0/G1 arrest and suppressed cell growth in gastric carcinoma cells. As our microarray analyses showed that E2F3, a cell cycle regulator, was inhibited by EBV infection, we hypothesized that miR-BART1-3p regulates E2F3. Luciferase assays revealed that miR-BART1-3p directly targeted the 3'-UTR of E2F3 mRNA. Both E2F3 mRNA and encoded protein levels were reduced following miR-BART1-3p transfection. In contrast, E2F3 expression in AGS-EBV cells transfected with a miR-BART1-3p inhibitor was enhanced. As E2F3 has been shown to regulate the expression of highly conserved miR-17-92 clusters in vertebrates, we examined whether this expression is affected by miR-BART1-3p, which can downregulate E2F3. The expression of E2F3, miR-17-92a-1 cluster host gene (MIR17HG), and miR-17-92 cluster miRNAs was significantly reduced in EBV-associated gastric carcinoma (EBVaGC) patients compared with EBV-negative gastric carcinoma (EBVnGC) patients. Further, miR-BART1-3p as well as the siRNA specific to E2F3 inhibited the expression of the miR-17-92 cluster, while inhibition of miR-BART1-3p enhanced the expression of the miR-17-92 cluster in cultured GC cells. Our results suggest a possible role of miR-BART1-3p in cell cycle regulation and in regulation of the miR-17-92 cluster through E2F3 suppression.

Effect of 5α-reductase inhibitors on the efficiency of thulium:yttrium-aluminium-garnet (RevoLix®) vaporesection for treating benign prostatic hyperplasia.

Purpose: Preoperative use of 5α-reductase inhibitors (5ARIs) may cause fibrosis of the prostate tissue and reduce the efficiency of thulium laser surgery for treating benign prostate hyperplasia (BPH). Thus, we investigated the effects of preoperative 5ARI use in this setting. Materials and Methods: This retrospective study examined 184 patients who underwent thulium laser surgery for BPH during 2012-2017. Patients were grouped according to their 5ARI use in order to compare their preoperative and intraoperative characteristics and subsequent outcomes. Surgical efficiency was assessed using vaporesection efficiency. The total operation time, vaporesection time and prostate volume change were measured. Results: The 5ARI+ group included 83 patients (45.1%) and the 5ARI- group included 101 patients (54.9%). There were no significant differences in the two groups' preoperative characteristics, postoperative prostate size, thulium laser energy use, or prostate volume reduction rate. However, relative to the 5ARI- group, the 5ARI+ group had a significant shorter total operative time (65.0 min vs. 70.0 min, p=0.013) and a significantly shorter vaporesection time (48.0 min vs. 54.0 min, p=0.014), which resulted in significantly higher vaporesection efficiency in the 5ARI+ group (0.66 mL/min vs. 0.51 mL/min, p<0.001). Both groups exhibit significant improvements in their quality of life score and International Prostate Symptom Score during the 12-month follow-up. Conclusions: In contrast with our expectations, the preoperative use of 5ARI increased the efficiency of thulium laser surgery for BPH. Thus, it may not be necessary to stop 5ARI treatment before performing thulium laser surgery in this setting.

Comprehensive Multi-Omics Analysis Reveals Aberrant Metabolism of Epstein-Barr-Virus-Associated Gastric Carcinoma.

The metabolic landscape of Epstein-Barr-virus-associated gastric cancer (EBVaGC) remains to be elucidated. In this study, we used transcriptomics, metabolomics, and lipidomics to comprehensively investigate aberrant metabolism in EBVaGC. Specifically, we conducted gene expression analyses using microarray-based data from gastric adenocarcinoma epithelial cell lines and tissue samples from patients with clinically advanced gastric carcinoma. We also conducted complementary metabolomics and lipidomics using various mass spectrometry platforms. We found a significant downregulation of genes related to metabolic pathways, especially the metabolism of amino acids, lipids, and carbohydrates. The effect of dysregulated metabolic genes was confirmed in a survival analysis of 3951 gastric cancer patients. We found 57 upregulated metabolites and 31 metabolites that were downregulated in EBVaGC compared with EBV-negative gastric cancer. Sixty-nine lipids, mainly ether-linked phospholipids and triacylglycerols, were downregulated, whereas 45 lipids, mainly phospholipids, were upregulated. In total, 15 metabolisms related to polar metabolites and 15 lipid-associated pathways were involved in alteration of metabolites by EBV in gastric cancer. In this work, we have described the metabolic landscape of EBVaGC at the multi-omics level. These findings could help elucidate the mechanism of EBVaGC oncogenesis.

Effect of prostate size on pathological outcome and biochemical recurrence after radical prostatectomy for prostate cancer: is it correlated with serum testosterone level?

OBJECTIVE: To examine whether prostate size is associated with pathological outcome and biochemical recurrence (BCR) after radical prostatectomy (RP) in patients with prostate cancer, and to evaluate whether it is correlated with serum testosterone level. PATIENTS AND METHODS: The study comprised 579 men treated with RP for prostate cancer between June 1991 and March 2008, with a prostate-specific antigen level of <20 ng/mL. We assessed the associations of prostate size (volume), measured using magnetic resonance imaging, and serum testosterone concentration, with adverse pathological outcomes and BCR. RESULTS: There was a positive correlation between preoperative prostate volume and prostate weight (r= 0.685, P < 0.001). On multivariate analysis, prostate volume was inversely associated with the outcomes of high-grade prostate cancer (P= 0.044), extracapsular extension (P= 0.011) and BCR (P= 0.016). There was also a positive correlation between serum testosterone level and prostate volume (r= 0.136, P= 0.043). Multivariate analysis showed that lower serum testosterone levels correlated with adverse pathological stage and a pathological Gleason score of ≥ 8 (P= 0.042). However, there was no relationship between serum testosterone level and BCR after adjusting for covariates. CONCLUSIONS: Men with smaller prostates had unfavourable pathological findings and were at greater risk of progression after RP. Low serum testosterone levels were not associated with tumour progression. Therefore, another mechanism, aside from hormonal factors, might be involved in unfavourable outcomes in patients with a small prostate.