title: MicroRNA-144 regulates cancer cell proliferation and cell-cycle transition in acute lymphoblastic leukemia through the interaction of FMN2.
abstract: BACKGROUND
  In the present study, we explored the functional roles of microRNA-144 (miR-144) upregulation and downregulation in human acute lymphoblastic leukemia (ALL).
  
  
  METHODS
  Gene expression of miR-144 was examined using the quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) in both ALL cell lines and T-leukemic cells of ALL patients. In ALL cell lines Molt-3 and Jurkat cells, miR-144 was either upregulated or downregulated through lentiviral transduction. The subsequent effects of miR-144 upregulation or downregulation on ALL proliferation, cell-cycle transition and in vivo xenograft were assessed. A possible downstream target of miR-144, human formin-2 (FMN2), was assessed by a dual-luciferase activity assay, qRT-PCR and western blotting. FMN2 was then overexpressed in miR-144-upregulated Molt-3 and Jurkat cells to determine its effect on miR-144 induced tumor suppression on ALL proliferation and cell-cycle transition.
  
  
  RESULTS
  MiR-144 was significantly downregulated in both ALL cell lines and T-leukemic cells of ALL patients. Lentiviral transfection successfully induced miR-144 upregulation or downregulation in Molt-3 and Jurkat cells without affecting cell viability. Functional assays demonstrated that miR-144 upregulation suppressed ALL proliferation and cell-cycle transition in vitro, as well as the growth of Jurkat xenograft in vivo, whereas miR-144 downregulation had no functional effect on ALL development. Multiple approaches confirmed that FMN2 was the downstream target of miR-144 in ALL. Finally, overexpressing FMN2 reversed the inhibitory effects of miR-144-upregulation on ALL proliferation and cell-cycle transition.
  
  
  CONCLUSIONS
  MiR-144 functions as a tumor suppressor in ALL, very likely through the inverse regulation of its target gene FMN2.
authors.forename: Jie
authors.initials: J
authors.lastname: Jin
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Xu
authors.initials: X
authors.lastname: Zhou
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Hematology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D000080865:Formins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019169:Jurkat Cells; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
chemical_list: C587953:Fmn2 protein, human; D000080865:Formins; C554293:MIRN144 microRNA, human; D035683:MicroRNAs; D008840:Microfilament Proteins; D009687:Nuclear Proteins
keywords: FMN2; acute lymphoblastic leukemia; cell-cycle transition; miR-144; proliferation; xenograft