Project description:The transcription factor AP4/TFAP4/AP-4 is a ubiquitously expressed basic helix-loop-helix leucine-zipper (bHLH-LZ) transcription factor, which forms homodimer that binds to the consensus E-box motif 5-CAGCTG-3. Prostatic adenocarcinoma (PAC), also known as prostate cancer, is the second most common malignancy of men with 914,000 new cases and approximately 258,000 deaths worldwide in 2008. The goal of this study is to identify the target genes of AP4 in prostate cancer. Our results demonstrated that the genes regulated by AP4 are involved in a variety of biological functions, such as proliferation and invasion. We used microarrays to detail the different expression of genes in AP4 knockdown and overexpression and identified distinct classes of up-regulated genes during this process.
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: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
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.