MiR-182 is Overexpressed in Head and Neck Squamous Cell Carcinomas Leading to Downregulation of Specific Transcripts
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ABSTRACT: This study correlated miR expression with predicted targets to determine those miRs that both downregulated a subset of their predicted targets and showed differential expression in cancer samples compared to controls Case: Control with HNSCC tumors and uvulopalatopharyngoplasty (UPPP) samples
Project description:This study integrated Affymetrix SNPchip data for CNV estimation, Affymetrix HuEx1.0 data for gene expression estimation, and Illumina HumanMethylation27k BeadChip data for promoter methylation to estimate pathway activity Case:Control with HNSCC tumors and uvulopalatopharyngoplasty (UPPP) samples
Project description:This study integrated Affymetrix SNPchip data for CNV estimation, Affymetrix HuEx1.0 data for gene expression estimation, and Illumina HumanMethylation27k BeadChip data for promoter methylation to estimate pathway activity. Case:Control with HNSCC tumors and uvulopalatopharyngoplasty (UPPP) samples
Project description:P493-6 contain a tet repressible MYC contruct. In the presense of tetracycline, MYC levels are great reduced and the cells cease to cycle. Gene expression was compared between high and low MYC expressing cells P493-6 cells were grown in both the presence and absence of tetracycline. RNA was extracted and gene expression analysis was performed using exon arrays
Project description:Neuronal activity-dependent gene expression plays important roles in neural plasticity. We use electroconvulsive stimulation (ECS) as an in vivo model for neuronal activation to identify genes that are regulated by neuronal activity. Dentate gyri (DG) were microdissected 4 hours after sham or ECS treatment for gene expression profiling. 4 total samples were analysed (2 for each condition). Averaged expression values between sham and ECS samples were pair-wise compared.
Project description:siRNA knock-down of ZNF genes determined to impact gastrointestinal stromal tumor response to imatinib were used to determine functional significance of ZNFs and identify key targets related to imatinib resistance. exploratory array design to identify candidate effector genes for targeted study
Project description:Epigenetic events, including covalent post-translational modification of histones, have frequently been demonstrated to play critical roles in tumor development and progression. The transcriptional coactivator, p300/CBP, possesses both histone acetyltransferase (HAT) activity as well as scaffolding properties that directly influence transcriptional activation of targeted genes. We have used a recently reported small molecule inhibitor of p300 HAT activity, C646, to explore the specific contribution of p300/CBP HAT activity to tumor development and progression. We find that C646 inhibits the growth of lineage-specific tumor cell lines including human melanomas through direct transcriptional regulation of cell cycle regulatory proteins. Further evaluation of the p300 HAT transcriptome in human melanoma cells using comprehensive gene expression profiling reveals that p300 HAT activity globally promotes cell cycle progression, nucleosome assembly, and the DNA damage checkpoint through direct transcriptional regulatory mechanisms. Additionally, C646 promotes sensitivity to DNA damaging agents leading to enhanced apoptosis of melanoma cells following combination treatment with cisplatin. Together our data suggest that p300 HAT activity regulates critical growth regulatory pathways in tumors and may serve as a novel therapeutic target for melanoma and other malignancies by promoting cellular responses to DNA damaging agents. Keywords: p300, small molecule inhibitor, melanoma WM35 cells grown under normal culture conditions were treated for 6 and 24 hours with compound C646 to block p300 HAT activity. A vehicle control (DMSO) was included at each time point. RNA was extracted from all 4 samples using the Qiagen RNeasy kit. RNA quality check, labeling, hybridization, initial data processing and analysis was performed by the JHMI Microarray Core Facility. Affymetrix GeneChip Human Exon 1.0 ST Array was used for this study.
Project description:Derailed gene expression programs within the developing nervous system, encompassing both transcriptional and posttranscriptional processes, can cause diverse neurodevelopmental diseases (NDD). The NDD FOXG1-syndrome lacks full understanding of the mechanistic role of its eponymous gene product. While it is known that FOXG1 acts in part at the chromatin by binding to regulative regions, it is unclear what factors control its presence at specific sites. Long non-coding RNAs (lncRNAs) can mediate site-directed transcription factor binding, but their potential role in FOXG1-syndrome has not been described. Here, we show that FOXG1 localisation is regulated at selected loci through the lncRNA Pantr1. We identified FOXG1 as an upstream transcriptional activator of Pantr1 in human and mice. Further, we discovered that FOXG1 has the ability to associate with RNAs. Both, transcriptional regulation of Pantr1 by FOXG1 and association of both partners, build up a regulative network that impacts the localisation of FOXG1 at selected genomic loci. Specifically, Pantr1 facilitates cooperative presence of FOXG1/NEUROD1 at specific sites, and Pantr1 reduction leads to redistribution of FOXG1 to comparably more generic binding sites. The rescue of impaired dendritic outgrowth upon FOXG1 reduction by simultaneous overexpression of Pantr1 underlines the importance of the FOXG1/Pantr1 regulative network.
Project description:Transactive response DNA-binding protein of 43 kDa (TDP-43), a heterogeneous nuclear ribonucleoprotein (hnRNP) with diverse activities, is a common denominator in several neurodegenerative disorders including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Orthologs of TDP-43 exist from mammals to invertebrates, but their functions in lower organisms remain poorly understood. Here we systematically studied mutant Caenorhabditis elegans lacking the nematode TDP-43 ortholog, TDP-1. To understand the global gene expression regulation induced by the loss of tdp-1, the C. elegans transcriptomes were compared between the N2 WT animals and the tdp-1(ok803lf) mutant. Transcriptional profiling demonstrated that the loss of TDP-1 altered expression of genes functioning in RNA processing and protein folding. These results suggest that the C. elegans TDP-1 as an RNA-processing protein may have a role in the regulation of protein homeostasis and aging. Global gene expression profiling was performed to compare the transcriptome of wild-type (N2) Caenorabditis elegans and that of tdp-1(ok803) loss-of-function mutant. We analyzed mixed stages of Caenorabditis elegans, wild-type N2 versus tdp-1(ok803), using the Affymetrix C. elegans genome array. Three biological replicates were performed.
Project description:Long non-coding RNAs (lncRNA) have been identified as key regulators of tumorigenesis and development. We aim to explore the biological functions and molecular mechanisms of lncRNA MIR200CHG in breast cancer. We found that MIR200CHG is highly expressed in breast cancer tissues and is related to the tumor size and histopathological grade. In vitro and in vivo experiments confirmed that MIR200CHG can promote breast cancer proliferation, invasion, and drug resistance. MIR200CHG directly binds to the transcription factor Y-box binding protein-1 (YB-1), and inhibits its ubiquitination and degradation. MIR200CHG regulates YB-1 phosphorylation at serine 102, thereby affecting the expression of genes related to tumor cell proliferation, apoptosis, invasion, and drug resistance. Additionally, MIR200CHG partially affects the expression of miR-200c/141-3p encoded by its intron region. Therefore, MIR200CHG can promote the proliferation, invasion, and drug resistance of breast cancer by interacting with and stabilizing YB-1, and has the potential to become a target for breast cancer treatment.