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GSE120855
Homo sapiens
7 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Human transcriptome array analysis of human cord blood mononuclear leokocytes from neonates exposed to histological chorioamnionitis and compared with healthy neonates
Publication Title
Histological Chorioamnionitis Induces Differential Gene Expression in Human Cord Blood Mononuclear Leukocytes from Term Neonates.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina HiSeq 2500
Description
The host innate immune response is the first line of defense against pathogens and is orchestrated by the concerted expression of genes induced by microbial stimuli. Deregulated expression of these genes is linked to the initiation and progression of numerous diseases associated with exacerbated inflammation. Here, we identify Topoisomerase 1 (Top1) as a critical positive regulator of RNA polymerase II (RNAPII) transcriptional activity at pathogen-induced genes. Notably, depletion or chemical inhibition of Top1 suppresses the host response against replicating Influenza and Ebola viruses as well as bacterial products. As a result, therapeutic pharmacological inhibition of Top1 protects mice from death in experimental models of chemical- and pathogen-induced lethal inflammation. Our results indicate that Top1 inhibition could be used as therapy against life threatening infections characterized by an acutely exacerbated immune response. Overall design: RNA seq was performed on Ebola (Wild type and mutant) infected or uninfected THP-1 cells in the presence of DMSO or Camptothecin
Publication Title
Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Screening small molecules and drugs for activity to modulate alternative splicing, we found that amiloride, distinct from four other intracellular pH-affecting analogues, could normalize the splicing of BCL-X, HIPK3 and RON/MISTR1 transcripts in human hepatocellular carcinoma Huh-7 cells. To elucidate the underlying mechanisms, our proteomic analyses of amiloride-treated cells detected hypo-phosphorylation of splicing factor SF2/ASF and also decreased levels of SRp20 and two un-identified SR proteins. We further observed decreased phosphorylation of AKT, ERK1/2 and PP1, while increased phosphorylation of p38 and JNK, suggesting that amiloride treatment down-regulated kinases and up-regulated phosphatases in the signal pathways known to affect the splicing factor protein phosphorylation. The amiloride effects of splicing factor protein hypo-phosphorylation andnormalizedoncogenic RNA splicing were both abrogated by pre-treatment with a PP1 inhibitor. We then performed global exon array analysis of Huh-7 cells treated with amiloride for 24 hours. Using gene array chips (Affymetrix GeneChip Human Exon 1.0 ST Array of >518000 exons of 42974 genes) for exon array analysis (set parameters of correlation coefficient 0.7, splicing index -1.585 , and log2 ratio -1.585), we found that amiloride influenced the splicing patterns of 551 genes involving at least 584 exons, which included 495 known protein-coding genes involving 526 exons, many of which play key roles in functional networks of ion transport, extracellular matrix, cytoskeletons and genome maintenance. Cellular functional analyses revealed subsequent invasion and migration defects, cell cycle disruption, cytokinesis impairment, and lethal DNA degradation in amiloride-treated Huh-7 cells. This study thus provides mechanistic underpinnings for exploiting small molecule modulation of abnormal RNA splicing for cancer therapeutics.
Publication Title
Small molecule amiloride modulates oncogenic RNA alternative splicing to devitalize human cancer cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
Alternative splicing is a mechanism for increasing the protein variety of a limited number of genes. Studies have shown that aberrant regulations of the alternative splicing of apoptotic gene transcripts may contribute to the development of cancer. In this study, we isolated 4ß-Hydroxywithanolide E (4bHWE) from the traditional herb Physalis peruviana, and analyzed its biological effects in cancer cells. The results demonstrated that 4bHWE modulates the alternative splicing of apoptotic genes (e.g., HIPK3, SMAC/DIABLO, and SURVIVIN), changes the expression level of splicing factors (e.g., hnRNP C1/C2, ASF/SF2, SRp20, and SRp55), and induces histone tail posttranslational modifications (e.g., H3K27me1, H3K27me2, H3K36me3, and H3K79me1). Pretreatment with okadaic acid to inhibit protein phosphatase-1 could partly relieve the effects of 4bHWE on the alternative splicing of HIPK3 and SMAC/DIABLO transcripts, as well as on the dephosphorylation of ASF/SF2. Genome-wide detection of alternative splicing further indicated that several other apoptosis-related genes are also regulated by 4bHWE, including APAF1, CARP-1, and RIPK1. Moreover, we extended our study to apoptosis-associated molecules, detecting an increasing level of CASPASE-3 activity and cleavage of poly ADP-ribose polymerase in 4bHWE-induced apoptosis. Furthermore, in vivo experiments showed that the treatment of tumor-bearing mice with 4bHWE resulted in a marked decrease of tumor size and weight. Taken together, this study is the first to show that 4bHWE affects alternative splicing through the modulations of splicing factors, providing a novel view of the antitumor mechanism of 4bHWE. Overall design: Examination of the global genes with altered alternative splicing in 4bHWE-treated Huh-7 cells.
Publication Title
4β-Hydroxywithanolide E Modulates Alternative Splicing of Apoptotic Genes in Human Hepatocellular Carcinoma Huh-7 Cells.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We demonstrate that GLUT4 up-regulation significantly increased cell migration and invasion in lower magligance head and neck cancer cell lines in vitro.
Publication Title
Glucose transporter 4 promotes head and neck squamous cell carcinoma metastasis through the TRIM24-DDX58 axis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The orthotopic transplantation of human OEC-M1 cells in immune-compromised mice was established to feasibly study tumorigenesis and lymph node metastasis of OSCC.
Publication Title
Insulin-like growth factor-independent insulin-like growth factor binding protein 3 promotes cell migration and lymph node metastasis of oral squamous cell carcinoma cells by requirement of integrin β1.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To exmaine the PTHLH stimulated genes in Ca9-22 cells, we preformed the Affymetrix Human Genome U133 Plus 2.0 Array with empty vector or PTHLH expression vector. The raw data were normalized by GeneSpring GX software and up-load with raw values.
Publication Title
Parathyroid Hormone-Like Hormone is a Poor Prognosis Marker of Head and Neck Cancer and Promotes Cell Growth via RUNX2 Regulation.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 50 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
The early-onset breast cancer patients (age 40) often display higher incidence of axillary lymph node metastasis, and poorer five-year survival than the late-onset patients. To identify the genes and molecules associated with poor prognosis of early-onset breast cancer, we examined gene expression profiles from paired breast normal/ tumor tissues, and coupled with Gene Ontology and public data base analysis. Our data showed that the expression of GAS7b gene was lower in the early-onset breast cancer patients as compared to the elder patients. We found that GAS7 was associated with CYFIP1 and WAVE2 complex to suppress breast cancer metastasis via blocking CYFIP1 and Rac1 protein interaction, actin polymerization, and 1-integrin/FAK/Src signaling. We further demonstrated that p53 directly regulated GAS7 gene expression, which was inversely correlated with p53 mutations in breast cancer specimens. Our study uncover a novel regulatory mechanism of p53 in early-onset breast cancer progression through GAS7-CYFIP1 mediated signaling pathways.
Publication Title
Wild-type p53 upregulates an early onset breast cancer-associated gene GAS7 to suppress metastasis via GAS7-CYFIP1-mediated signaling pathway.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To examine the transcription targets of RUNX2 in OSCC cells, we preformed the Affymetrix Human Genome U133 Plus 2.0 Array with ectopic RUNX2 or empty vectors in Ca9-22 cells.
Publication Title
Dysregulation of RUNX2/Activin-A Axis upon miR-376c Downregulation Promotes Lymph Node Metastasis in Head and Neck Squamous Cell Carcinoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 48 Downloadable Samples
- Illumina HiSeq 2500
Description
We have developed a protocol to generate hematopoietic and cardiac derivatives in vitro by Mesp1 induction in ES cells. The goal of this study is to analyze the heterogeneity of Mesp1+ mesoderm by single-cell RNA-seq Overall design: 48 Mesp1-induced single cells were captured using the Fluidigm C1 microfluidic system. RNA extraction, RT and cDNA amplication were then performed according to the manufacturer's manual.
Publication Title
Heterogeneity of Mesp1+ mesoderm revealed by single-cell RNA-seq.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples