Objective: The expression of DACH1 was frequently lost in human breast cancer, which significantly correlated with poor prognosis. Herein, we aim to investigate its underlying mechanisms.Methods: The expression of miR-217 was detected by Taqman PCR. The mRNA and protein level of DACH1 were investigated by real time PCR and western blot. The dual-luciferase reporter system was used to determine the direct interaction between miR-217 and DACH1. A series of gain&loss of function assays were performed to measure the affects of miR-217 on tumor proliferation and cell cycle distribution.Results: Compared to that in normal breast samples, the expression of miR-217 was significantly upregulated in breast cancer tissues. High level of miR-217 was notably correlated with highly histological grade, the triple negative subtype and advanced tumor stage. Moreover, the expression of miR-217 was negatively correlated with the expression of DACH1. The results of dual-luciferase reporter assay demonstrated that miR-217 directly targets and inhibits the transcriptive activity of DACH1. In vitro, treatment with miR-217 mimics significantly suppressed the proliferation of MCF-7 cells, induced G1 phase arrest and inhibited the expression of cyclin D1; while these effects were significantly reversed by the restoration of DACH1. In MDA-MB-231 cells, treatment with miR-217 inhibitors enhanced the cellular proliferation, promoted cell cycle progression and upregulated the expression of cyclin D1, which were neutralized by the pre-treatment of siRNA-DACH1. In vivo, inhibition of miR-217 significantly suppressed the xenografts growth and downregulated the expression of cyclin D1.Conclusion: We found that miR-217 was commonly overexpressed in breast cancer, which could enhance tumor proliferation via promoting cell cycle progression. Moreover, the DACH1 (the cell fate determination factor) was identified as a novel target of miR-217. Our results proposed inhibiting miR-217 to be a potent therapeutic strategy for breast cancer.
The aim of this study was to determine whether oxymatrine has a protective effect against acute pancreatitis (AP) in a rat model of L-arginine-induced AP. AP was induced by two intraperitoneal injections of L-arginine (250 mg/100 g) at a 1-h interval. Oxymatrine (50 mg/kg) was administered every 6 h after the induction of AP. Oxymatrine significantly reduced the plasma amylase, D-lactic acid and tumor necrosis factor alpha concentration, serum diamine oxidase and lipase activity, and pancreatic myeloperoxidase activity, which were increased in AP rats (P < 0.05). In addition, the pancreatic CD45 expression and the expression of claudin-1, but not zonula occludens-1 (ZO-1) and occludin, in the intestinal tissues were significantly reduced after the induction of AP. However, oxymatrine increased the expression of claudin-1 and CD45, but did not alter the expression of ZO-1 and occludin. In conclusion, our results demonstrated that oxymatrine is potentially capably of protecting against L-arginine-induced AP and attenuating AP-associated intestinal barrier injury by up-regulation of claudin-1.
Bladder cancer is one of the most common cancer types globally. The UBC® Rapid Test is a potential novel diagnostic method for bladder cancer, but studies into its accuracy have produced inconsistent results. Thus, the present meta-analysis was conducted in order to determine the overall accuracy of the UBC® Rapid Test in detecting bladder cancer. A comprehensive literature search was conducted using MEDLINE, Embase, Cochrane Library, Web of Science, Chinese WanFang and the China National Knowledge Infrastructure databases for relevant studies. Quality assessment of diagnostic accuracy studies 2 was used to assess the quality of each included study. The diagnostic accuracy of the UBC® Rapid Test was evaluated by pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and the area under the curve (AUC). In addition, Deeks' funnel plot was used to evaluate potential publication bias. Eight studies were included in the quantitative meta-analysis. The results were as follows: Sensitivity 0.59 [95% confidence interval (CI), 0.55–0.62], specificity 0.76 (95% CI, 0.72–0.80), PLR 2.55 (95% CI, 1.75–3.70), NLR 0.56 (95% CI, 0.46–0.67), DOR 4.88 (95% CI, 2.82–8.45) and AUC 0.70 (95% CI, 0.67–0.74). According to the present results, the UBC® rapid test is highly accurate in the diagnosis of bladder cancer, however, further studies with better-designed and larger samples are required in order to support the results of the present study.
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