MicroRNA-192 regulates cell proliferation and cell cycle transition in acute myeloid leukemia via interaction with CCNT2

Int J Hematol. 2017 Aug;106(2):258-265. doi: 10.1007/s12185-017-2232-2. Epub 2017 Apr 13.


MicroRNAs (miRNAs) are a class of small non-coding RNAs approximately 18-22 nucleotides in length, which play an important role in malignant transformation. The roles of miR-192 as an oncogene or tumor suppressor in solid tumors have been previously reported. However, little is known about the role of miR-192 in human acute myeloid leukemia. The results of the present study indicate that miR-192 is significantly downregulated in specimens from acute myeloid leukemia patients. Functional assays demonstrated that overexpression of miR-192 in NB4 and HL-60 cells significantly inhibited cell proliferation compared with that in control cells, and induced G0/G1 cell cycle arrest, cell differentiation, and apoptosis in vitro. Dual-luciferase reporter gene assays showed that miR-192 significantly suppressed the activity of a reporter gene containing the wild type 3'-UTR of CCNT2, but it did not suppress the activity of a reporter gene containing mutated 3'-UTR of CCNT2. QRT-PCR and Western blot assays showed that miR-192 significantly downregulated the expression of CCNT2 in human leukemia cells. Exogenous expression of CCNT2 attenuated the cell cycle arrest induced by miR-192 in NB4 and HL-60 cells. Collectively, miR-192 inhibits cell proliferation and induces G0/G1 cell cycle arrest in AML by regulating the expression of CCNT2.

Keywords: Acute myeloid leukemia; CCNT2; Cell cycle; miR-192.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Apoptosis / genetics
  • Cell Cycle / genetics*
  • Cell Cycle Checkpoints / genetics
  • Cell Proliferation / genetics*
  • Cell Transformation, Neoplastic / genetics*
  • Cyclin T / genetics*
  • Cyclin T / physiology*
  • Down-Regulation
  • Gene Expression
  • HL-60 Cells
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology*
  • MicroRNAs / genetics*
  • MicroRNAs / physiology*


  • 3' Untranslated Regions
  • CCNT2 protein, human
  • Cyclin T
  • MIRN192 microRNA, human
  • MicroRNAs