title: Retinoic acid induces HL-60 cell differentiation via the upregulation of miR-663.
abstract: BACKGROUND
  Differentiation of the acute myeloid leukemia (AML) cell line HL-60 can be induced by all trans-retinoic acid (ATRA); however, the mechanism regulating this process has not been fully characterized.
  
  
  METHODS
  Using bioinformatics and in vitro experiments, we identified the microRNA gene expression profile of HL-60 cells during ATRA induced granulocytic differentiation.
  
  
  RESULTS
  Six microRNAs were upregulated by ATRA treatment, miR-663, miR-494, miR-145, miR-22, miR-363* and miR-223; and three microRNAs were downregulated, miR-10a, miR-181 and miR-612. Additionally, miR-663 expression was regulated by ATRA. We used a lentivirus (LV) backbone incorporating the spleen focus forming virus (SFFV-F) promoter to drive miR-663 expression, as the CMV (Cytomegalovirus) promoter is ineffective in some lymphocyte cells. Transfection of LV-miR-663 induced significant HL-60 cell differentiation in vitro.
  
  
  CONCLUSIONS
  Our results show miR-663 may play an important role in ATRA induced HL-60 cell differentiation. Lentivirus delivery of miR-663 could potentially be used directly as an anticancer treatment in hematological malignancies.
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Jian
authors.forename: Zhao Wen
authors.initials: ZW
authors.lastname: Li
authors.forename: Tao Yan
authors.initials: TY
authors.lastname: Fang
authors.forename: Wang
authors.initials: W
authors.lastname: Jian
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhuan
authors.forename: Liao Xin
authors.initials: LX
authors.lastname: Mei
authors.forename: Wu Shui
authors.initials: WS
authors.lastname: Yan
authors.forename: Ni
authors.initials: N
authors.lastname: Jian
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013155:Spleen Focus-Forming Viruses / Q000235:genetics; D013997:Time Factors; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C552243:MIRN663 microRNA, human; D035683:MicroRNAs; D014212:Tretinoin