Silencing of circTASP1 inhibits proliferation and induces apoptosis of acute myeloid leukaemia cells through modulating miR-515-5p/HMGA2 axis

J Cell Mol Med. 2021 Aug;25(15):7367-7380. doi: 10.1111/jcmm.16765. Epub 2021 Jul 1.

Abstract

Acute myeloid leukaemia (AML) is a common hematopoietic disease that is harmful to the lives of children and adults. CircRNAs are aberrantly expressed in the haematologic malignancy cells. However, the expression of circTASP1 and its function in AML remain unclear. In this study, we showed that circTASP1 was significantly up-regulated in AML peripheral blood samples and cells. Knockdown of circTASP1 inhibited proliferation and promoted apoptosis of HL60 and THP-1 cells in vitro. Bioinformatics prediction and luciferase reporter assay proved that circTASP1 sponged miR-515-5p and negatively regulated miR-515-5p expression in HL60 and THP-1 cells. High mobility group A2 (HMGA2) was proved to be a downstream target of miR-515-5p. The rescue experiments confirmed that knockdown of circTASP1 inhibited proliferation and induced apoptosis by modulating miR-515-5p/HMGA2 pathway. Moreover, the in vivo experiment indicated that knockdown of circTASP1 suppressed tumour growth. In conclusion, circTASP1 acts as a sponge for miR-515-5p to regulate HMGA2, thereby promoting proliferation and inhibiting apoptosis during AML progression. Thus, circTASP1 has the potential to be explored as a therapeutic target for AML treatment.

Keywords: CircTASP1; HMGA2; apoptosis; miR-515-5p; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Apoptosis*
  • Cell Proliferation
  • Endopeptidases / genetics*
  • Female
  • HMGA2 Protein / genetics
  • HMGA2 Protein / metabolism*
  • Humans
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / metabolism*
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • RNA, Circular / genetics*
  • RNA, Circular / metabolism
  • THP-1 Cells

Substances

  • HMGA2 Protein
  • HMGA2 protein, human
  • MIRN515 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Endopeptidases
  • taspase1, human