title: Regulation of RAB5C is important for the growth inhibitory effects of MiR-509 in human precursor-B acute lymphoblastic leukemia.
abstract: MicroRNAs (miRs) regulate essentially all cellular processes, but few miRs are known to inhibit growth of precursor-B acute lymphoblastic leukemias (B-ALLs). We identified miR-509 via a human genome-wide gain-of-function screen for miRs that inhibit growth of the NALM6 human B-ALL cell line. MiR-509-mediated inhibition of NALM6 growth was confirmed by 3 independent assays. Enforced miR-509 expression inhibited 2 of 2 additional B-ALL cell lines tested, but not 3 non-B-ALL leukemia cell lines. MiR-509-transduced NALM6 cells had reduced numbers of actively proliferating cells and increased numbers of cells undergoing apoptosis. Using miR target prediction algorithms and a filtering strategy, RAB5C was predicted as a potentially relevant target of miR-509. Enforced miR-509 expression in NALM6 cells reduced RAB5C mRNA and protein levels, and RAB5C was demonstrated to be a direct target of miR-509. Knockdown of RAB5C in NALM6 cells recapitulated the growth inhibitory effects of miR-509. Co-expression of the RAB5C open reading frame without its 3' untranslated region (3'UTR) blocked the growth-inhibitory effect mediated by miR-509. These findings establish RAB5C as a target of miR-509 and an important regulator of B-ALL cell growth with potential as a therapeutic target.
authors.affiliation: Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Yee Sun
authors.initials: YS
authors.lastname: Tan
authors.affiliation: Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America; Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America; Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: MinJung
authors.initials: M
authors.lastname: Kim
authors.affiliation: Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America; Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, United States of America; Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Tami J
authors.initials: TJ
authors.lastname: Kingsbury
authors.affiliation: Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America; Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, United States of America; Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America; Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Curt I
authors.initials: CI
authors.lastname: Civin
authors.affiliation: Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America; Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Wen-Chih
authors.initials: WC
authors.lastname: Cheng
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D059807:S Phase Cell Cycle Checkpoints; D020696:rab5 GTP-Binding Proteins / Q000235:genetics*
chemical_list: C571982:MIRN509 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C427755:RAB5C protein, human; D020696:rab5 GTP-Binding Proteins