Role of Circular RNA DLEU2 in Human Acute Myeloid Leukemia

Mol Cell Biol. 2018 Sep 28;38(20):e00259-18. doi: 10.1128/MCB.00259-18. Print 2018 Oct 15.

Abstract

In the current study, we were interested in exploring the molecular mechanism of circular RNA DLEU2 (circRNA-DLEU2) (hsa_circ_0000488) and microRNA 496 (miR-496), as well as PRKACB, in human acute myeloid leukemia (AML) cell activities. The RNA expression levels of circRNA-DLEU2, hsa-miR-496, and PRKACB were assessed by quantitative real-time PCR (qRT-PCR). The proliferation and apoptosis abilities of the cells were determined by CCK8 assay and flow cytometry analysis. Target relationships between circRNA-DLEU2 and miR-496, as well as PRKACB, were analyzed by luciferase reporter assay and probe assay. Immunoblotting assays were used to detect the protein expression level of PRKACB. We also did <i>in vivo</i> experiments to observe tumor formation after overexpression of circRNA-DLEU2. Our data showed that circRNA-DLEU2 was upregulated in AML tissues and cells, which promoted AML cell proliferation and inhibited cell apoptosis. circRNA-DLEU2 promoted AML tumor formation <i>in vivo</i> miR-496 was inhibited by circRNA-DLEU2 and was downregulated in AML tissues. circRNA-DLEU2 inhibited miR-496 expression and promoted PRKACB expression. miR-496 antagonized the effects of PRKACB on MOLM-13 cell proliferation and apoptosis. Collectively, circRNA-DLEU2 accelerated human AML by suppressing miR-496 and promoting PRKACB expression.

Keywords: AML; PRKACB; circRNA-DLEU2; hsa-miR-496.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Apoptosis / genetics
  • Base Sequence
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / genetics
  • Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Heterografts
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Middle Aged
  • Models, Genetic
  • RNA / genetics*
  • RNA / metabolism
  • RNA, Circular
  • RNA, Long Noncoding
  • Transferases
  • Tumor Suppressor Proteins / genetics*
  • Up-Regulation

Substances

  • DLEU2 lncRNA, human
  • MIRN496 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA, Long Noncoding
  • Tumor Suppressor Proteins
  • RNA
  • Transferases
  • Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
  • PRKACB protein, human