title: MiR-27a functions as a tumor suppressor in acute leukemia by regulating 14-3-3θ.
abstract: MicroRNAs (miRs) play major roles in normal hematopoietic differentiation and hematopoietic malignancies. In this work, we report that miR-27a, and its coordinately expressed cluster (miR-23a∼miR-27a∼miR-24-2), was down-regulated in acute leukemia cell lines and primary samples compared to hematopoietic stem-progenitor cells (HSPCs). Decreased miR-23a cluster expression in some acute leukemia cell lines was mediated by c-MYC. Replacement of miR-27a in acute leukemia cell lines inhibited cell growth due, at least in part, to increased cellular apoptosis. We identified a member of the anti-apoptotic 14-3-3 family of proteins, which support cell survival by interacting with and negatively regulating pro-apoptotic proteins such as Bax and Bad, as a target of miR-27a. Specifically, miR-27a regulated 14-3-3θ at both the mRNA and protein levels. These data indicate that miR-27a contributes a tumor suppressor-like activity in acute leukemia cells via regulation of apoptosis, and that miR-27a and 14-3-3θ may be potential therapeutic targets.
authors.affiliation: Center for Stem Cell Biology and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA. KScheibner@som.umaryland.edu
authors.forename: Kara A
authors.initials: KA
authors.lastname: Scheibner
authors.forename: Brianne
authors.initials: B
authors.lastname: Teaboldt
authors.forename: Mary Claire
authors.initials: MC
authors.lastname: Hauer
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Chen
authors.forename: Srujana
authors.initials: S
authors.lastname: Cherukuri
authors.forename: Yin
authors.initials: Y
authors.lastname: Guo
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Kelley
authors.forename: Zhenqiu
authors.initials: Z
authors.lastname: Liu
authors.forename: Maria R
authors.initials: MR
authors.lastname: Baer
authors.forename: Shelly
authors.initials: S
authors.lastname: Heimfeld
authors.forename: Curt I
authors.initials: CI
authors.lastname: Civin
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; D051017:Apoptosis Regulatory Proteins; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins