TGF-β1-regulated miR-3691-3p targets / 亚洲男科学杂志(英文版)

Transforming growth factor-β1 (TGF-β1) acts as a tumor promoter in advanced prostate cancer (PCa). We speculated that microRNAs (miRNAs) that are inhibited by TGF-β1 might exert anti-tumor effects. To assess this, we identified several miRNAs downregulated by TGF-β1 in PCa cell lines and selected miR-3691-3p for detailed analysis as a candidate anti-oncogene miRNA. miR-3691-3p was expressed at significantly lower levels in human PCa tissue compared with paired benign prostatic hyperplasia tissue, and its expression level correlated inversely with aggressive clinical pathological features. Overexpression of miR-3691-3p in PCa cell lines inhibited proliferation, migration, and invasion, and promoted apoptosis. The miR-3691-3p target genes E2F transcription factor 3 (E2F3) and PR domain containing 1, with ZNF domain (PRDM1) were upregulated in miR-3691-3p-overexpressing PCa cells, and silencing of E2F3 or PRDM1 suppressed PCa cell proliferation, migration, and invasion. Treatment of mice bearing PCa xenografts with a miR-3691-3p agomir inhibited tumor growth and promoted tumor cell apoptosis. Consistent with the negative regulation of E2F3 and PRDM1 by miR-3691-3p, both proteins were overexpressed in clinical PCa specimens compared with noncancerous prostate tissue. Our results indicate that TGF-β1-regulated miR-3691-3p acts as an anti-oncogene in PCa by downregulating E2F3 and PRDM1. These results provide novel insights into the mechanisms by which TGF-β1 contributes to the progression of PCa.

Inhibition of pathogenic Leptospira on phagocytosis of peritoneal macrophages of guinea pigs / 上海第二医科大学学报

Objective To investigate the effects of different Leptospira strains on phagocytosis of peritoneal macrophages of guinea pigs,and explore the role of innate immune in the pathogenesis of leptospirosis. Methods Peritoneal macrophages of guinea pigs were infected in vitro by three different Leptospira strains,the virulent Leptospira interrogans serovar Lai type strain Lai,the avirulent L.interrogans serovar Lai type strain IPAV,and the nonpathogenic L.biflexa serovar Patoc type strain PatocⅠ,respectively,and heat inactivated Staphylococcus epidermidis was added 0.5,1.5,3 and 6 h after infection and incubated for 30 min.The effect of Leptospira on the phagocytosis of macrophage was evaluated by the inactivated Staphylococcus epidermidis phagocytosis rate and phagocytosis index.Phagocytosis and ultrastructure of peritoneal macrophages were observed by transmission electron microscopy 3 h after infection,and changes of cytoskeleton of the macrophages were observed by laser scanning confocal microscopy. Results The phagocytic rates and phagocytic indexes of strain Lai,strain IPAV and strain PatocⅠinfection groups were significantly lower than those of control group 3 h and 6 h after infection(P