MicroRNA-144 regulates cancer cell proliferation and cell-cycle transition in acute lymphoblastic leukemia through the interaction of FMN2

J Gene Med. 2017 Jun;19(6-7). doi: 10.1002/jgm.2898.

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.

Keywords: FMN2; acute lymphoblastic leukemia; cell-cycle transition; miR-144; proliferation; xenograft.

MeSH terms

  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Formins
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Jurkat Cells
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology*

Substances

  • Fmn2 protein, human
  • Formins
  • MIRN144 microRNA, human
  • MicroRNAs
  • Microfilament Proteins
  • Nuclear Proteins