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The FOXO1 transcription factor plays a central role in the proliferation and survival of B cells at several stages of differentiation. B cell malignancies, with exception of classical Hodgkin lymphoma, maintain expression of FOXO1 at levels characteristic for their non-malignant counterparts. Extensive expression profiling had revealed that Burkitt lymphoma (BL) show many characteristics of the dark zone (DZ) germinal center (GC) B cell program. Here we show that FOXO1 knockdown inhibits proliferation of human BL cell lines. The anti-proliferative effect of the FOXO1 knockdown is associated with the repression of the DZ B cell program including expression of MYB, CCND3, RAG2, BACH2, and CXCR4. In addition, the induction of signaling pathways of the light zone (LZ) program like NF-κB and PI3K-AKT was observed. Using a rescue experiment we identified downregulation of the proto-oncogene MYB as a critical factor contributing to the antiproliferative effect of FOXO1 knockdown. In an attempt to estimate the feasibility of pharmacological FOXO1 repression, we found that the small molecular weight FOXO1 inhibitor AS1842856 induces cell death and growth arrest in BL cell lines at low concentrations. Interestingly, we found that overactivation of FOXO1 also induces growth inhibition in BL cell lines, indicating the importance of a tight regulation of FOXO1 activity in BL.
Pubmed ID: 31557894
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Biomedical technology research center and training resource for the study of the structure of partially ordered biological molecules, complexes of biomolecules and cellular structures under conditions similar to those present in living cells and tissues. The goal of research at BioCAT is to determine the detailed structure and mechanism of action of biological systems at the molecular level. The techniques used are X-ray fiber diffraction, X-ray solution scattering and X-ray micro-emission and micro-absorption spectroscopy, with an emphasis on time-resolved studies and the development of novel techniques.
View all literature mentionsDatabase which provides on-line searching of microarray datasets generated from rat spinal cord after contusion injury. Both the primary injury site and a site 5 mm distal to the injury site were assayed. Tissue was obtained from Long Evans rats subject to spinal cord contusion injury using the MASCIS impactor (formerly known as the NYU impactor). RNA expression was assayed at the site of injury and distal to the site of injury using the Affymetrix Rat Neuro U34 chip.
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View all literature mentionsSoftware package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
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