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GSE26535
Homo sapiens
6 Downloadable Samples
Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
OBJECTIVE: Glial progenitor cells are abundant in adult human white matter. This study was designed to identify signaling pathways regulating their self-renewal and fate.
Publication Title
Complementary patterns of gene expression by human oligodendrocyte progenitors and their environment predict determinants of progenitor maintenance and differentiation.
Sample Metadata Fields
Sex, Age, Disease
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- Mus musculus
- 12 Downloadable Samples
Illumina HiSeq 4000
Description
Previous studies have demonstrated that E-proteins induce AID expression in activated B cells. Here we have examined the role of Id3 in germinal center (GC) cells. We found that Id3 expression is high in follicular B-lineage cells but declines in GC cells. Immunized mice depleted for Id3 expression displayed a block in germinal center B cell maturation, showed reduced numbers of marginal zone B cells and class switched cells, were associated with decreased antibody titers and lower numbers of plasma cells. In vitro Id3-depleted B cells displayed a defect in class switch recombination. Whereas AID levels were not altered in Id3-depleted activated B cells, the expression of a subset of genes encoding for signaling components of antigen receptor, cytokine receptor and chemokine receptor mediated signaling was significantly impaired. We propose that during the GC reaction Id3 levels decline to activate the expression of genes encoding for signaling components that mediate B cell receptor and or cytokine-mediated signaling to promote the differentiation of GC B cells. Overall design: B cells derived from control and CD19-Cre;Id3loxP/loxP mice were activated in vitro in the presence of LPS and IL-4 for 24 or 48 hours. RNA was isolated from naïve as well as activated control and CD19-Cre;Id3loxP/loxP mice and analyzed by RNA-seq, in duiplicate.
Publication Title
Id3 Orchestrates Germinal Center B Cell Development.
Sample Metadata Fields
Specimen part, Cell line, Subject
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- Mus musculus
- 20 Downloadable Samples
- Illumina HiSeq 2500
Description
It is now well established that the E- and Id-protein axis regulates multiple steps in lymphocyte development. However, it remains unknown as to how E- and Id-proteins mechanistically enforce and maintain the naïve T cell fate. Here we show that Id2 and Id3 suppressed the development and expansion of innate-variant TFH cells. Innate-variant TFH cells required MHC Class I-like signalling and were associated with germinal center B cell development. We found that Id2 and Id3 induced Foxo1 and Foxp1 expression to antagonize the activation of TFH transcription signature. We show that Id2 and Id3 acted upstream of the Hif1a/Foxo/AKT/mTORC1 pathway as well as the c-myc/p19Arf module to control cellular expansion and activation. We found that mice depleted for Id2 and Id3 expression developed colitis and aß T cell lymphomas. Lymphomas depleted for Id2 and Id3 expression displayed elevated levels of c-myc whereas p19Arf abundance declined. Transcription signatures of Id2- and Id3-depleted lymphomas revealed similarities with genetic deficiencies associated with Burkitt lymphoma. We propose that in response to antigen receptor and/or cytokine signaling the E-Id protein axis modulates the activities of the PI3K-AKT-mTORC1-Hifa and c-myc/p19Arf pathways to control cellular expansion and homeostatic proliferation. Overall design: RNA-seq data of 5 of wild type CD4SP cells, 3 of wild type Tfh cells, 3 of Id3-/- CD4SP cells, 3 of Id2-/-Id3-/-(dKO) CD4SP cells, and 6 of Id2-/-Id3-/- lymphoma cells.
Publication Title
The E-Id protein axis modulates the activities of the PI3K-AKT-mTORC1-Hif1a and c-myc/p19Arf pathways to suppress innate variant TFH cell development, thymocyte expansion, and lymphomagenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Illumina HiSeq 2000
Description
The tumor suppressor genes EAF2 and p53 are frequently dysregulated in prostate cancers. Recently, we reported that concurrent p53 nuclear staining and EAF2 downregulation were associated with high Gleason score. Combined loss of EAF2 and p53 in a murine model induced prostate tumors, and concurrent knockdown of EAF2 and p53 in prostate cancer cells enhanced proliferation and migration, further suggesting that EAF2 and p53 could functionally interact in the suppression of prostate tumorigenesis. Here, RNA-seq analyses identified differentially regulated genes in response to concurrent knockdown of p53 and EAF2. Several of these genes were associated with the STAT3 signaling pathway, and this was verified by significantly increased p-STAT3 immunostaining in the Eaf2-/-p53-/- mouse prostate. STAT3 knockdown abrogated the stimulation of C4-2 cell proliferation by concurrent knockdown of EAF2 and p53. Furthermore, immunostaining of p-STAT3 was increased in human prostate cancer specimens with EAF2 downregulation and/or p53 nuclear staining. Our findings suggest that simultaneous inactivation of EAF2 and p53 can act to activate STAT3 and drive prostate tumorigenesis. Overall design: C4-2 prostate cancer cells treated with siEAF2 and/or sip53 mRNA profiles were generated by deep sequencing, using Illumina HiSeq 2000.
Publication Title
EAF2 and p53 Co-Regulate STAT3 Activation in Prostate Cancer.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples