title: Notch-mediated repression of miR-223 contributes to IGF1R regulation in T-ALL.
abstract: To identify microRNAs regulated by oncogenic Notch signaling, we performed microarray-based miRNA profiling of T-cell acute lymphoblastic leukemia (T-ALL) cells before and after treatment with γ-secretase inhibitor (GSI) to block Notch signaling. We show miR-223 levels increase after GSI treatment suggesting that active Notch signaling represses miR-223 expression. We also demonstrate that insulin-like growth factor-1 receptor (IGF1R) is regulated by miR-223 in this context, but observe no apparent effects on cell growth by overexpression or knock-down of miR-223 alone. We conclude that miR-223 contributes to IGF1R regulation, but may act in concert with other genes and/or microRNAs to alter T-ALL biology.
authors.affiliation: Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Samuel
authors.initials: S
authors.lastname: Gusscott
authors.forename: Florian
authors.initials: F
authors.lastname: Kuchenbauer
authors.forename: R Keith
authors.initials: RK
authors.lastname: Humphries
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Weng
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology; D046228:Microarray Analysis; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D054928:Validation Studies as Topic
chemical_list: D035683:MicroRNAs; D017526:Receptor, IGF Type 1; D051881:Receptor, Notch1; C525067:MIR223, human; C497761:NOTCH1 protein, human