title: miR-181a promotes G1/S transition and cell proliferation in pediatric acute myeloid leukemia by targeting ATM.
abstract: OBJECTIVE
  Abnormal expression of miRNAs is intimately related to a variety of human cancers. The purpose of this study is to confirm the expression of miR-181a and elucidate its physiological function and mechanism in pediatric acute myeloid leukemia (AML).
  
  
  METHODS
  Pediatric AML patients and healthy controls were enrolled, and the expression of miR-181a and ataxia telangiectasia mutated (ATM) in tissues were examined using quantitative PCR. Moreover, cell proliferation and cell cycle were evaluated in several cell lines (HL60, NB4 and K562) by using flow cytometry after transfected with miR-181a mimics and inhibitors, or ATM siRNA and control siRNA. Finally, ATM as the potential target protein of miR-181a was examined.
  
  
  RESULTS
  We found that miR-181a was significantly increased in pediatric AML, which showed an inverse association with ATM expression. Overexpressed miR-181a in cell lines significantly enhanced cell proliferation, as well as increased the ratio of S-phase cells by miR-181a mimics transfection in vitro. Luciferase activity of the reporter construct identified ATM as the direct molecular target of miR-181a. ATM siRNA transfection significantly enhanced cell proliferation and increased the ratio of S-phase cells in vitro.
  
  
  CONCLUSIONS
  The results revealed novel mechanism through which miR-181a regulates G1/S transition and cell proliferation in pediatric AML by regulating the tumor suppressor ATM, providing insights into the molecular mechanism in pediatric AML.
authors.affiliation: Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Liao
authors.affiliation: Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Peng
authors.affiliation: Department of Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Xuequn
authors.initials: X
authors.lastname: Luo
authors.affiliation: Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
authors.forename: Ziyan
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Department of Hematology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, 510623, Guangdong Province, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Hematology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, 510623, Guangdong Province, China. luoxul64@126.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
mesh_terms: D017209:Apoptosis; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002453:Cell Cycle; D049109:Cell Proliferation; D002648:Child; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: ATM; Acute myeloid leukemia; Cell proliferation; MicroRNA; Tumor suppressor