MicroRNA-370-3p inhibits cell proliferation and induces chronic myelogenous leukaemia cell apoptosis by suppressing PDLIM1/Wnt/β-catenin signaling

Neoplasma. 2020 May;67(3):509-518. doi: 10.4149/neo_2020_190612N506. Epub 2020 Jan 27.

Abstract

Growing evidence has suggested that microRNA-370-3p (miR-370-3p) is downregulated and acts as a suppressor in several cancers. However, the role of miR-370-3p in chronic myeloid leukemia (CML) remains unknown. Here, the expression level and molecular mechanism of miR-370-3p in CML were investigated. Firstly, the expression of miR-370-3p has markedly decreased in the peripheral blood mononuclear cells (PBMCs) of patients with CML and in cell lines. Moreover, miR-370-3p in CML cells upregulated and downregulated proliferation and apoptosis, respectively. Notably, miR-370-3p directly targeted the 3'-untranslated region of PDZ and LIM domain protein 1 (PDLIM1). A negative correlation was observed between the levels of miR-370-3p and PDLIM1 in the PBMCs of patients with CML and healthy volunteers. PDLIM1 was shown to have an oncogenic role in CML cells by promoting proliferation and suppressing apoptosis. Finally, the miR-370-3p-PDLIM1-Wnt/β-catenin signaling axis was indicated to play an important role in CML progression.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • LIM Domain Proteins / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
  • Leukocytes, Mononuclear
  • MicroRNAs / genetics*
  • Transcription Factors / genetics*
  • Wnt Signaling Pathway*

Substances

  • LDB2 protein, human
  • LIM Domain Proteins
  • MIRN370 microRNA, human
  • MicroRNAs
  • Transcription Factors