title: MicroRNAs contribute to promyelocyte apoptosis in As2O3-treated APL cells.
abstract: BACKGROUND
  Arsenic trioxide (As2O3), an ancient drug used in traditional Chinese medicine, has substantial anticancer activities, especially in the treatment of patients suffering from acute promyelocytic leukemia (APL); however the underlying mechanisms are not well understood.
  
  
  METHODS
  MTT assay was used to detect the cell viability. Flow Cytometry analysis and caspase-3 activity assay were used to measure apoptosis of APL cells. Caspase-3 and Bax levels were analyzed by western blot and let-7d and miR-766 levels were determined by real-time RT-PCR.
  
  
  RESULTS
  As2O3 significantly inhibited cell viability and induced apoptosis in APL cells. Several microRNAs, including let-7d and miR-766, were dysregulated in APL cells treated with As2O3. The expression of caspase-3 and Bax, which are targets of let-7d and miR-766, respectively, were up-regulated in As2O3 treated cells. Transfection of let-7d and miR-766 into NB4 cells decreased the expression of caspase-3 and Bax, respectively. Correspondingly, transfection of these microRNAs increased NB4 cell viability. As2O3 induced degradation of promyelocytic leukemia (PML), and then induced the down-regulation of both let-7d and miR-766 in NB4 cells.
  
  
  CONCLUSIONS
  We construct a dysregulated microRNA network involved in As2O3-induced apoptosis in APL. Targeting this network may be a new strategy for the prevention of side effects associated with APL treatment with As2O3.
authors.affiliation: Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin, P. R. China.
authors.forename: Haihai
authors.initials: H
authors.lastname: Liang
authors.forename: Xuelian
authors.initials: X
authors.lastname: Li
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Shaonan
authors.initials: S
authors.lastname: Yu
authors.forename: Zhidan
authors.initials: Z
authors.lastname: Xu
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Gu
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Pan
authors.forename: Tianyu
authors.initials: T
authors.lastname: Li
authors.forename: Meiyu
authors.initials: M
authors.lastname: Hu
authors.forename: Hairong
authors.initials: H
authors.lastname: Cui
authors.forename: Xue
authors.initials: X
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chaoqian
authors.initials: C
authors.lastname: Xu
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Lu
authors.forename: Baofeng
authors.initials: B
authors.lastname: Yang
authors.forename: Hongli
authors.initials: H
authors.lastname: Shan
mesh_terms: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001483:Base Sequence; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000378:metabolism*; D010087:Oxides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D001152:Arsenicals; C575913:MIRN766 microRNA, human; D035683:MicroRNAs; D010087:Oxides; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D000077237:Arsenic Trioxide