26 Let-7g was slightly, but not significantly, increased after LIF stimulation, which is in contrast to previous descriptions on let-7g in cancer. In hepatocellular carcinoma, ectopic expression of let-7g inhibits cell migration and growth.27 In gastric cancer, low let-7g is associated with unfavorable outcome in overall survival independent of clinical covariates, including depth of invasion, lymph-node metastasis, and stage.28 LIF-stimulated buy SCH772984 JEG-3 cells expressed significantly higher levels of miR-93, which

is in line with previous observations on tumors. In human glioblastoma, miR-93 suppresses integrin-β8 expression, which promotes tumor growth and angiogenesis.29 In human T-cell leukemia virus 1, miR-93 targets the mRNA for tumor protein 53–induced nuclear protein 1 (TP53INP1), which is a tumor suppressor protein.30 In our experiments, miR-9 did not change considerably. In human embryonic stem cell-derived neural progenitors, loss of miRNA-9 reduces proliferation and increases migration.31 On the

other hand, miR-9 targets E-cadherin, RXDX-106 chemical structure which is a suppressor of metastasization and angiogenesis. Its high expression in breast cancer is correlated with the malign properties.32 In JEG-3 cells, LIF significantly downregulated miR-141. Repression of miR-141 induces invasiveness of breast cancer cells by targeting the endothelial mesenchymal transition activators ZEB1 and ZEB2, which downregulate E-cadherin expression.18 Also in colorectal cancer, miR-141 negatively correlates with migration and invasion.9 A different function has been observed for miR-141 in gastric cancer cells, where its over-expression by the application of its precursors Thiamet G inhibited the proliferation.33 In contrast, it is upregulated in nasopharyngeal carcinoma, where it positively correlates with proliferation, migration, and invasion.34 In our hands, silencing of miR-141 inhibits proliferation of JEG-3 choriocarcinoma cells, which goes in line

with these results. The observed strong impact of LIF on various miRNA in JEG-3 choriocarcinoma cells underlines the expected involvement of miRNAs in the regulation of essential functions in trophoblastic cells and thus in tuning placentation and other crucial processes in reproduction and pregnancy. The project has been supported by the German Research Foundation (DFG, project Ma1550/7-1). DMMP has a Ph.D. grant from the regional graduate academy of the Friedrich-Schiller-University Jena, Germany. “
“Type 1 diabetes is an autoimmune disease whose clinical onset signifies a lifelong requirement for insulin therapy and increased risk of medical complications.