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 in vivo 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 in vivo 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