Circular RNA (circRNA) is a large group of RNA family extensively existed in cells and tissues. High-throughput sequencing provides a way to view circRNAs across different samples, especially in various diseases. However, there is still no comprehensive database for exploring the cancer-specific circRNAs. We collected 228 total RNA or polyA(-) RNA-seq samples from both cancer and normal cell lines, and identified 272 152 cancer-specific circRNAs. A total of 950 962 circRNAs were identified in normal samples only, and 170 909 circRNAs were identified in both tumor and normal samples, which could be further used as non-tumor background. We constructed a cancer-specific circRNA database (CSCD, http://gb.whu.edu.cn/CSCD). To understand the functional effects of circRNAs, we predicted the microRNA response element sites and RNA binding protein sites for each circRNA. We further predicted potential open reading frames to highlight translatable circRNAs. To understand the association between the linear splicing and the back-splicing, we also predicted the splicing events in linear transcripts of each circRNA. As the first comprehensive cancer-specific circRNA database, we believe CSCD could significantly contribute to the research for the function and regulation of cancer-associated circRNAs.

Apigenin (APG) is an edible plant-derived flavonoid that shows modest antitumor activities in vitro and in vivo. APG treatment results in cell growth arrest and apoptosis in various types of tumors by modulating several signaling pathways. In the present study, we evaluated interactions between APG and TRAIL in non-small cell lung cancer (NSCLC) cells. We observed a synergistic effect between APG and TRAIL on apoptosis of NSCLC cells. A549 cells and H1299 cells were resistant to TRAIL treatment alone. The presence of APG sensitized NSCLC cells to TRAIL-induced apoptosis by upregulating the levels of death receptor 4 (DR4) and death receptor 5 (DR5) in a p53-dependent manner. Consistently, the pro-apoptotic proteins Bad and Bax were upregulated, while the anti-apoptotic proteins Bcl-xl and Bcl-2 were downregulated. Meanwhile, APG suppressed NF-κB, AKT and ERK activation. Treatment with specific small-molecule inhibitors of these pathways enhanced TRAIL-induced cell death, mirroring the effect of APG. Furthermore, using a mouse xenograft model, we demonstrated that the combined treatment completely suppressed tumor growth as compared with APG or TRAIL treatment alone. Our results demonstrate a novel strategy to enhance TRAIL-induced antitumor activity in NSCLC cells by APG via inhibition of the NF-κB, AKT and ERK prosurvival regulators.

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The aim of this study was to investigate the effects of glutamine on the histomorphology of the liver, oxidative stress and nuclear factor-κB (NF-κB) expression in the development of nonalcoholic fatty liver disease (NAFLD). NAFLD was induced in rats by a high-fat diet, and rats in the treatment group were subjected to oral administration of glutamine (1 g/kg/day). Rats from the treatment, model and normal control groups were assessed after 8 and 12 weeks (n=6 per group at each time-point). The levels of glutathione (GSH), malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) in the liver, and the liver histopathology and NF-κB protein 65 (p65) expression in the liver were assessed. Compared with the control group under the same experimental period, the MDA and TNF-α levels in the liver, the hepatic steatosis and the hepatic expression of NF-κB p65 were significantly higher in the model and the treatment groups (P<0.05), while the GSH levels in the liver were significantly lower (P<0.05). These indices improved significantly in the treatment group compared with the model group (P<0.05). In conclusion, glutamine reduces the degree of oxidative stress in the liver, inhibits NF-κB p65 expression and improves hepatic steatosis. Glutamine has a certain protective effect in NAFLD.