Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
Project description:Contrary to many reports that antiplatelet agents inhibit cancer growth and metastasis, reports of increased mortality from the development of new solid tumors in patients receiving long-term antiplatelet therapy raise questions about the effects of antiplatelet agents on cancer. Therefore, we have investigated the direct effects on cancer cells in the absence of platelets, assuming long-term antiplatelet therapy. Treatment of cancer cells with four antiplatelet reagents (aspirin and three P2Y12 inhibitors: clopidogrel, prasugrel, and ticagrelor) inhibited the proliferation of cancer cells, similar to the results of previous studies. Surprisingly, there was no difference in the aspirin-treated group, but the motility of cancer cells was significantly increased when treated with purinergic P2Y12 inhibitors. Therefore, gene expression profiles were examined to investigate the effect of antiplatelet reagents on cancer cell mobility. As a result, SERPINE1 was identified as a common gene associated with cancer cell motility and cell death in three groups. SERPINE1 increased by antiplatelet reagent treatment was found to be involved in cell mobility by activating FAK-p38-MMP1. These results show that purine antiplatelet reagents reduce cancer cell proliferation but increase cell motility by inducing SERPINE1 and MAPK-MMP1 signaling pathways. Therefore, we suggest that SERPINE1 could be used as a new target gene for the development and metastasis of cancer in patients with long-term antiplatelet therapy.
Project description:We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3’ and/or 5’ end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5’ differences and in support of this we report that a 5’ isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5’ isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes