miRNA-650 exerts anti-leukemia activity by inhibiting cell proliferation through Gfi1 targeting

Tumori. 2018 Oct;104(5):369-374. doi: 10.5301/tj.5000643. Epub 2018 May 9.

Abstract

Background:: Acute myeloid leukemia (AML) is the most common malignancy of the bone marrow with a high mortality. Recent advances in high-throughput sequencing have led to the identification of various miRNAs implicated in the pathogenesis of AML. We found in this study that miR-650, a miRNA that was traditionally considered to participate in the onset of hepatocellular carcinoma, might play a significant role in AML development and progression.

Methods:: qRT-PCR was used to detect the expression of miR-650 and Gfi1 in AML patients and healthy controls. Next, a luciferase assay was conducted to verify the target effect of miR-650 on Gfi1. Moreover, the CCK-8 assay was performed to evaluate the effect of miR-650 on the proliferation of AML cells in the presence and absence of Gfi1.

Results:: miR-650 was downregulated in AML whereas Gfi1 was upregulated. miR-650 could negatively regulate Gfi1 via direct targeting of its 3'-UTR, which was confirmed by luciferase assay. In addition, overexpression of miR-650 reduced cell proliferation in K562 cells, whereas an increase in cell proliferation was observed when K562 cells were transfected with miR-650 inhibitor, which was compromised in response to the knockdown of Gfi1.

Conclusions:: Our research demonstrated that miR-650 modulates cell proliferation in AML through affecting the expression of Gfi1, which occurs by direct target action.

Keywords: Acute myeloid leukemia; Gfi1; Proliferation; miR-650.

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Case-Control Studies
  • Cell Proliferation*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Follow-Up Studies
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology*
  • MicroRNAs / genetics*
  • Prognosis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • GFI1 protein, human
  • MIRN650 microRNA, human
  • MicroRNAs
  • Transcription Factors