title: Upregulation of microRNA-125b contributes to leukemogenesis and increases drug resistance in pediatric acute promyelocytic leukemia.
abstract: BACKGROUND
  Although current chemotherapy regimens have remarkably improved the cure rate of pediatric acute promyelocytic leukemia (APL) over the past decade, more than 20% of patients still die of the disease, and the 5-year cumulative incidence of relapse is 17%. The precise gene pathways that exert critical control over the determination of cell lineage fate during the development of pediatric APL remain unclear.
  
  
  METHODS
  In this study, we analyzed miR-125b expression in 169 pediatric acute myelogenous leukemia (AML) samples including 76 APL samples before therapy and 38 APL samples after therapy. The effects of enforced expression of miR-125b were evaluated in leukemic cell and drug-resistant cell lines.
  
  
  RESULTS
  miR-125b is highly expressed in pediatric APL compared with other subtypes of AML and is correlated with treatment response, as well as relapse of pediatric APL. Our results further demonstrated that miR-125b could promote leukemic cell proliferation and inhibit cell apoptosis by regulating the expression of tumor suppressor BCL2-antagonist/killer 1 (Bak1). Remarkably, miR-125b was also found to be up-regulated in leukemic drug-resistant cells, and transfection of a miR-125b duplex into AML cells can increase their resistance to therapeutic drugs,
  
  
  CONCLUSIONS
  These findings strongly indicate that miR-125b plays an important role in the development of pediatric APL at least partially mediated by repressing BAK1 protein expression and could be a potential therapeutic target for treating pediatric APL failure.
authors: Key Laboratory of Gene Engineering of Ministry of Education, State Key Laboratory, for Biocontrol, Sun Yat-sen University, Guangzhou 510275, China.
authors: Hua
authors: H
authors: Zhang
authors: Xue-Qun
authors: XQ
authors: Luo
authors: Dan-Dan
authors: DD
authors: Feng
authors: Xing-Ju
authors: XJ
authors: Zhang
authors: Jun
authors: J
authors: Wu
authors: Yu-Sheng
authors: YS
authors: Zheng
authors: Xiao
authors: X
authors: Chen
authors: Ling
authors: L
authors: Xu
authors: Yue-Qin
authors: YQ
authors: Chen
mesh_terms: D000293:Adolescent; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D007223:Infant; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D049410:Luciferases, Renilla / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D016896:Treatment Outcome; D015854:Up-Regulation; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494772:BAK1 protein, human; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D050998:bcl-2 Homologous Antagonist-Killer Protein; D049410:Luciferases, Renilla