MiR-15a/16 regulates the growth of myeloma cells, angiogenesis and antitumor immunity by inhibiting Bcl-2, VEGF-A and IL-17 expression in multiple myeloma

Leuk Res. 2016 Oct:49:73-9. doi: 10.1016/j.leukres.2016.08.013. Epub 2016 Aug 28.

Abstract

miRNAs have been reported to be involved in the pathogenesis of many cancers. In this article, we investigated the role and the mechanisms of miR-15a/16 in the pathogenesis of multiple myeloma (MM). We found that miR-15a/16 was down-regulated in bone marrow-derived mononuclear cells (BM-MNCs) of newly diagnosed patients with MM and the downregulation of miR-15a/16 was correlated with International Staging System (ISS) stage. We then demonstrated miR-15a/16 inhibited myeloma cells proliferation, and increased apoptosis rate of U266 cells by suppressing the expression of anti-apoptosis protein Bcl-2. We also found miR-15a/16 could decrease VEGF-A and IL-17 levels in the supernatant of myeloma cells. These results indicate that miR-15a/16 may function as a tumor suppressor in MM through multiple regulatory mechanisms and they may be potential targets for the therapy of MM.

Keywords: Bcl-2; IL-17; Multiple myeloma; VEGF-A; miR-15a/16.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunity
  • Interleukin-17 / antagonists & inhibitors
  • Interleukin-17 / metabolism
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Middle Aged
  • Multiple Myeloma / immunology
  • Multiple Myeloma / pathology*
  • Neovascularization, Pathologic
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Interleukin-17
  • MIRN15 microRNA, human
  • MIRN16 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2
  • Vascular Endothelial Growth Factor A