GSE141402 Real-time quantitative PCR analysis for NF-kB related genes of mouse bone marrow with engrafted human leukemia cells after C-miR146a treatment

Contributors : Yu-Lin Su ; Xiuli Wang ; Mati Mann ; Tomasz Adamus ; Dayson Moreira ; Dongfang Wang ; Zhuoran Zhang ; Ching Ouyang ; Xin He ; Bin Zhang ; Piotr Swiderski ; Stephen Forman ; David Baltimore ; Ling Li ; Guido Marcucci ; Mark Boldin ; Marcin KortylewskiSeries Type : Expression profiling by RT-PCROrganism : Mus musculusNF- κB is a key regulator of inflammation and cancer progression, with important role in leukemogenesis. Despite therapeutic potential, targeting NF-κB using pharmacologic inhibitors proved challenging. Here, we describe a myeloid cell-selective NF-κB inhibitor using miR146a mimic oligonucleotide con jugated to a scavenger receptor (SR)/Toll-like receptor 9 (TLR9) agonist (C-miR146a). Unlike an unconjugated miR-146a, C-miR146a was rapidly internalized and delivered to cytoplasm of target myeloid cells and leukemic cells. C-miR146a reduced expression of classic miR-146a targets, IRAK1 and TRAF6, thereby blocking NF-κB activation in target cells. Intravenous injections of C-miR146a mimic to miR-146-deficient mice prevented excessive NF-κB activation in myeloid cells, thereby alleviating myeloproliferation and mice hypersensitivity to bacterial challenge. Importantly, C-miR146a showed effic acy in dampening severe inflammation in clinically relevant models of chimeric antigen receptor (CAR) T-cell-induced cytokine release syndrome (CRS). Systemic administration of C-miR146a oligonucleotide alleviated human monocyte-dependent releas...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by RT-PCR Mus musculus Source Type: research