Project description:Recent studies have implicated KDM3A, which catalyzes removal of H3K9 methylation, is associated with tumorigenesis. However, the biological role of KDM3A in multiple myeloma, has not been delineated. Here we identify KDM3A-KLF2-IRF4 axis dependence in multiple myeloma. We demonstrate that knockdown of KDM3A leads to apoptosis and significant growth inhibition in myeloma cells. Mechanistically, KDM3A directly regulates myeloma cell survival factor IRF4 expression through H3K9 demethylation at its promoter. We further show that KDM3A directly regulates KLF2 expression and that knockdown of KLF2 leads to growth inhibition in myeloma cells. The goal of this analysis is to identify genes whose expression changes after shRNA-mediated knockdown of KDM3A and KLF2 using the human U133 plus 2.0 Affymetrix GeneChip in myeloma cell line (RPMI8226). Two independent experiments were performed: 1. Myeloma cell line (RPMI8226) was transduced with either shRNAs targeting KDM3A (duplicate hairpins) or luciferase (control) in duplicate. The gene expression profiles of KDM3A knockdown cells were compared with that of control cells. A total of 6 RNA samples (4 KDM3A knockdown and 2 control) were analyzed. 2. Myeloma cell line (RPMI8226) was transduced with either shRNAs targeting KLF2 (duplicate hairpins) or luciferase (control) in duplicate. The gene expression profiles of KLF2 knockdown cells were compared with that of control cells. A total of 6 RNA samples (4 KLF2 knockdown and 2 control) were analyzed.
Project description:Recent studies have implicated KDM3A, which catalyzes removal of H3K9 methylation, is associated with tumorigenesis. However, the biological role of KDM3A in multiple myeloma, has not been delineated. Here we identify KDM3A-KLF2-IRF4 axis dependence in multiple myeloma. We demonstrate that knockdown of KDM3A leads to apoptosis and significant growth inhibition in myeloma cells. Mechanistically, KDM3A directly regulates myeloma cell survival factor IRF4 expression through H3K9 demethylation at its promoter. We further show that KDM3A directly regulates KLF2 expression and that knockdown of KLF2 leads to growth inhibition in myeloma cells. The goal of this analysis is to identify genes whose expression changes after shRNA-mediated knockdown of KDM3A and KLF2 using the human U133 plus 2.0 Affymetrix GeneChip in myeloma cell line (RPMI8226).
Project description:1) We identified the genes whose expression was up- and down-regulated by the adhesion to bone marrow stromal cells in human multiple myeloma cell line RPMI8226. 2) We identified the genes whose expression was up- and down-regulated by the PI3K inhibitor PF-04691502 in human multiple myeloma cell line RPMI8226. We isolated mRNA from the multiple myeloma cell line RPMI8226 under drug-resistant conditions, and subjected them to gene expression profiling using an Agilent GeneChip Array.
Project description:1) We identified the genes whose expression was up- and down-regulated by the adhesion to bone marrow stromal cells in human multiple myeloma cell line RPMI8226. 2) We identified the genes whose expression was up- and down-regulated by the PI3K inhibitor PF-04691502 in human multiple myeloma cell line RPMI8226.
Project description:Evaluation of anti-myeloma effects of inhibition of PRMT5, involved in arginine methylation. Three human multiple myeloma cell lines were treated with the PRMT5 inhibitor EPZ015938. Transcriptional profiles were compared to untreated controls.
