Project description:Analysis of MDA-MB-231 cells following TSA treatment or not. TSA regulates various miRNA expression in MDA-MB-231 cells.Results provide insight into the role of miRNAs-involved mechanisms underlying TSA-mediated effects on breast cancer stemness.
Project description:To explore how TSA-MSCexo improves myocardial ischemia-reperfusion injury, miRNA microarray analysis was used to screen differentially expressed miRNAs in MSCexo and TSA-MSCexo.
Project description:Endothelial progenitors represent one of the most promising cell-based strategies for vascular repair of ischemic tissue damage, including limb ischemia, myocardial infarction and stroke. We have shown that the transcription factor TAL1 regulates a transcription program that drives the migration and adhesion of ECFCs. Furthermore, treatment of ECFCs with the HDAC inhibitor TSA increases the expression of TAL1-dependent genes and promotes the migration, chemotaxis and adhesion of ECFCs. Finally, ex vivo treatment with TSA also improves the vascular repair properties of ECFCs in vivo when these cells are transplanted in a mouse model of hindlimb ischemia. The goal of this experiment was to test whether TSA treatment of ECFCs affect TAL1 genomic binding. TAL1 ChIP-sequencing was performed from ECFCs that have been treated or not TSA. As negative controls, we performed Mock-ChIP-seq from the same samples using normal IgG instead of the TAL1 antibody. Overall, we find that there is no change in TAL1 genomic binding in ECFCs upon TSA treatment.
Project description:In order to identify the TSA responsive genes, we performed a gene expression microarray analysis for the RNAs isolated from TSA-untreated and TSA-treated human keratinocytes
Project description:To explore TSA influence on human breast cancer cells, we attempt to analyze genes differentially expressed between TSA treated and untreated SKBR3 cells, which will hopefully provide clues for TSA target genes.
Project description:Treatment with the histone deacetylase inhibitor trichostatin a (TSA) changes the radial positioning of the CFTR gene in HeLa S3 cells. The gene relocates from the nuclear periphery to the nuclear interior. In Calu-3 cells the gene is located in the nuclear interior. To identifiy potential regulatory elements for the positioning of CFTR, the histone h3 and h4 acetylation patterns of untreated and TSA-treated HeLa S3 and untreated Calu-3 cells were determined by ChIP-chip. A CTCF site close to the CFTR promoter displayed consistent histone H3 hyperacetylation in TSA treated HeLa S3 cells and Calu-3 cells.
Project description:These data were used for prediction of neoantigens and minor histocompatibility mismatch antigens, which were subsequently used for design of a machine-learning algorithm for tumor-specific antigen (TSA) immunogenicity prediction. TSA vaccines are a growing area of study for cancer immunotherapy, but identification of clinically relevant targets remains a challenge. The study associated with these data provides the first description of a computational method for direct prediction of TSA immunogenicity trained entirely from validated TSA immunogenicity scores. This tool has allowed us to 1) predict for clinically efficacious TSA targets, 2) identify genomic correlates of TSA immunogenicity, and 3) demonstrate evidence of alternative out-of-frame TSAs which can promote anti-tumor immunity.
Project description:Histone deacetylase inhibitors (HDACi), such as Trichostatin A (TSA), hold enormous promise for the treatment of HCC. In this study, we investigated the effects of TSA treatment on a c-Myc-induced HCC model in mice. TSA treatment delayed the development of HCC, and liver function indicators such as ALT, AST, liver weight ratio, and spleen weight ratio indicated the effectiveness of TSA treatment. Oil red staining further demonstrated that TSA attenuated lipid accumulation in the HCC tissues of mice. Through mRNA sequencing, we identified that TSA mainly affected cell cycle and fatty acid degradation genes, with alcohol dehydrogenase 4 (ADH4) potentially being the core molecular downstream target. QPCR, immunohistochemistry, and western blot analysis revealed that ADH4 expression was repressed by c-Myc and recovered after TSA treatment both in vitro and in vivo. Furthermore, we observed that the levels of total NAD+ and NADH, NAD+, NAD+/NADH, and ATP concentration increased after c-Myc transfection in liver cells but decreased after TSA intervention. The levels of phosphorylated protein kinase B (p-AKT) and p-mTOR were identified as targets regulated by TSA, and they governed the ADH4 expression and the downstream regulation of total NAD+ and NADH, NAD+, NAD+/NADH, and ATP concentration. Overall, our study suggests that TSA has a therapeutic effect on c-Myc-induced HCC through the AKT-mTOR-ADH4 pathway.
Project description:We report the differential roles of an HDAC inhibitor-TSA during hESC nerual commitment. In the initiation of hESC differentiation, TSA could inhibit the downregulation of pluripotency genes to maintain pluripotency, whereas in the neural commitment stage, TSA could promote neural gene expression to assist hESC nerual determination.
Project description:Cardiac hypertrophy is characterized by an increase in heart size and profound gene expression changes. Pharmacological histone deacetylase (HDAC) inhibitors attenuate pathological cardiac remodeling and hypertrophic gene expression. Published literature has linked enzymes that mediates histone acetylation to pathogenesis, however, the role of histone acetylation to define hypertrophic gene regulatory events are not well understood. We used chromatin immunoprecipitation (ChIP) coupled with massive parallel sequencing (seq) to comprehensively examine genome-wide histone acetylation changes in a pre-clinical model of pathological cardiac hypertrophy by transverse aortic constricted (TAC). We examined the gene targets conferred by the prototypical HDAC inhibitor Trichostatin A (TSA). TSA induces genome-wide histone acetylation and deacetylation in the heart. Alterations to histone acetylation were found on genes involved in cardiac morphology such as cardiac contraction, collagen deposition, inflammation and extracellular matrix. Gene set enrichment analysis identified NF-kappa B (NFKB), as a transcription factor positively correlated with TAC and negatively correlated with TSA by ChIP-seq. Histone acetylation on the promoters of NKFB target genes was increased, consistent with gene activation. In contrast, the promoters of these genes were deacetylated by TSA in hypertrophic animals and reduced expression of NFKB target genes. Our results suggest a potential mechanism for TSA mediated cardioprotection conferred by histone deacetylation of target genes implicating the importance of inflammation. ChIP-seq profiles for histone acetylation in left ventricles of mice that develop cardiac hypertrophy and treated with HDAC inhibitors were generated by deep sequencing, using Illumina GAIIx.