title: MicroRNA-183 promotes cell proliferation via regulating programmed cell death 6 in pediatric acute myeloid leukemia.
abstract: OBJECTIVE
  The aim of this study was to investigate roles of microRNA (miR)-183 in pediatric acute myeloid leukemia (AML).
  
  
  METHODS
  miR-183 expression in bone marrow and patients' sera of childhood AML was detected by real-time quantitative PCR. Functions of miR-183 in malignant phenotypes of two leukemia cell lines were then evaluated. Additionally, putative targets of miR-183 were predicted using three miRNA target prediction algorithms and validated by luciferase reporter assay. Clinical relevance of miR-183 and its target gene were further determined.
  
  
  RESULTS
  miR-183 expression in bone marrow and patients' sera of childhood AML was both significantly higher than those in the corresponding normal controls (both P < 0.001). Enforced expression of miR-183 dramatically enhanced cell proliferation and G1/S transition, but inhibited cell apoptosis of leukemia cells. Bioinformatics prediction and luciferase reporter assay identified programmed cell death 6 (PDCD6) as a direct target gene of miR-183. Moreover, high serum miR-183 combined with low serum PDCD6 mRNA was significantly associated with French-American-British classification subtype M7 (P = 0.01) and unfavorable karyotypes (P = 0.006). Further multivariate analysis identified the combination of serum miR-183 and PDCD6 levels as an independent prognostic factor for both relapse-free and overall survivals. Functionally, re-introduction of PDCD6 markedly reversed the effects of miR-183 in cell cycle, proliferation and apoptosis of two leukemia cell lines.
  
  
  CONCLUSIONS
  Combined serum miR-183 and PDCD6 mRNA may serve as a novel prognostic biomarker for pediatric AML. Interestingly, miR-183 may function as an oncogene and may enhance cell proliferation by targeting PDCD6, implying a potential therapeutic target for this malignancy.
authors.affiliation: Department of Pediatrics, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, 223300, Jiangsu, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Huai'an Hospital Affiliated to Xuzhou Medical College and Huai'an Second People's Hospital, 62 Huaihai Road South, Huai'an, 223002, Jiangsu, China.
authors.forename: Dongjian
authors.initials: D
authors.lastname: Zuo
authors.affiliation: Department of Pediatrics, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, 223300, Jiangsu, China.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Pediatrics, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, 223300, Jiangsu, China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, 223300, Jiangsu, China.
authors.forename: Ze
authors.initials: Z
authors.lastname: Hong
authors.affiliation: Department of Pediatrics, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, 223300, Jiangsu, China. zrrhayy@sina.com.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016016:Proportional Hazards Models; D034622:RNA Interference; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; C533449:MIRN183 microRNA, human; D035683:MicroRNAs; C097753:PDCD6 protein, human
keywords: Pediatric acute myeloid leukemia; Prognosis; Programmed cell death 6; Proliferation; microRNA-183