Project description:We aimed to identify genes that are regulated by FGFR1 in brown adipose tissues of adult male ob/ob mice by injecting 1 mg/kg anti-FGFR1 agonistic antibody.
Project description:A series of experiments to establish a bovine developing mammary gland gene expression signature, identify genes differentially expressed in bovine lactating mammary gland, and to establish the false positive rate of the BMAM microarray Keywords = gene expression, differential expression, lactation, development, physiology, bovine, mammary, microarray, EST, cDNA Keywords: repeat sample
Project description:Oncogenic transformation of hematopoietic stem cells by chimeric fusion kinases causing constitutive activation of FGFR1 leads to a stem cell leukemia/lymphoma (SCLL) syndrome, accompanied by widespread dysregulation of gene activity. We now show that FGFR1 activation is associated with upregulation of MYC and pharmacological suppression of FGFR1 activation leads to downregulation of MYC and suppression of MYC target genes. Luciferase reporter assays demonstrate that FGFR1 can directly regulate MYC expression and this effect is enhanced in the presence of chimeric FGFR1 kinases. In SCLL cells, a truncated form of FGFR1 is generated by granzyme B cleavage of the chimeric kinases, producing a nucleus-restricted derivative that can bind MYC regulatory regions. Mutation of the granzyme B cleavage site prevents relocation to the nucleus but does not suppress MYC activation, suggesting additional mechanisms of MYC activation in the presence of cytoplasm-restricted chimeric kinases. We show that one of these mechanisms involves activating cytoplasmic STAT5, which upregulates MYC independent of the truncated FGFR1 kinase. Targeting MYC function using shRNA knockdown and 10054-F8 in SCLL cells leads to inhibition of cell proliferation and synergizes with the BGJ398 FGFR1 inhibitor, suggesting a combination therapy that could be used in the treatment of SCLL.
Project description:Purpose: Oncogenic transformation of hematopoietic stem cells by chimeric fusion kinases causing constitutive activation of FGFR1 leads to a stem cell leukemia/lymphoma (SCLL) syndrome, accompanied by widespread dysregulation of gene activity. The goals of this study are to use NGS-derived transcriptome profiling (RNA-seq) to identify genes regulated by FGFR1 fusion kinase in SCLL. Methods: Three different cell models for SCLL, respectively BBC2 (B cell lymphoblastic leukemia/lymphoma), ZNF112 (B cell lymphoblastic leukemia/lymphoma) and BCRF8C (myloid leukemia) were treated with selective FGFR1 kinase inhibitor,then the total RNA from treatment and viechel control were isolated for RNA-Seq analysis. Results: A global gene experssion change is generated, and provides fundamental information for demostration of molecular mechanisms in FGFR1 driven leukemogenesis.
Project description:Intervention type:DRUG. Intervention1:Huaier, Dose form:GRANULES, Route of administration:ORAL, intended dose regimen:20 to 60/day by either bulk or split for 3 months to extended term if necessary. Control intervention1:None.
Primary outcome(s): For mRNA libraries, focus on mRNA studies. Data analysis includes sequencing data processing and basic sequencing data quality control, prediction of new transcripts, differential expression analysis of genes. Gene Ontology (GO) and the KEGG pathway database are used for annotation and enrichment analysis of up-regulated genes and down-regulated genes.
For small RNA libraries, data analysis includes sequencing data process and sequencing data process QC, small RNA distribution across the genome, rRNA, tRNA, alignment with snRNA and snoRNA, construction of known miRNA expression pattern, prediction New miRNA and Study of their secondary structure Based on the expression pattern of miRNA, we perform not only GO / KEGG annotation and enrichment, but also different expression analysis.. Timepoint:RNA sequencing of 240 blood samples of 80 cases and its analysis, scheduled from June 30, 2022..
Project description:RNA-seq is a powerful tool to analyze differential expression of cellular pathways under different conditions. The goals of this study is to analyze the potential pathways involved in cellular defense against high glucose with or without FGFR1 knowdown.
