miR-186 inhibits cell proliferation in multiple myeloma by repressing Jagged1

Biochem Biophys Res Commun. 2016 Jan 15;469(3):692-7. doi: 10.1016/j.bbrc.2015.11.136. Epub 2015 Dec 8.

Abstract

MicroRNAs (miRNAs) are small, noncoding ribonucleic acids that regulate gene expression by targeting mRNAs for translational repression and degradation. Accumulating experimental evidence supports a causal role of miRNAs in hematology tumorigenesis. However, the specific functions of miRNAs in the pathogenesis of multiple myeloma (MM) remain to be established. In this study, we demonstrated that miR-186 is commonly downregulated in MM cell lines and patient MM cells. Ectopic expression of miR-186 significantly inhibited cell growth, both in vitro and in vivo, and induced cell cycle G0/G1 arrest. Furthermore, miR-186 induced downregulation of Jagged1 protein expression by directly targeting its 3'-untranslated region (3'-UTR). Conversely, overexpression of Jagged1 rescued cells from miR-186-induced growth inhibition. Our collective results clearly indicate that miR-186 functions as a tumor suppressor in MM, supporting its potential as a therapeutic target for the disease.

Keywords: Jagged1; Multiple myeloma; Proliferation; miR-186.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium-Binding Proteins / metabolism*
  • Cell Proliferation / genetics
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Jagged-1 Protein
  • Membrane Proteins / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Multiple Myeloma / genetics
  • Multiple Myeloma / metabolism*
  • Multiple Myeloma / pathology*
  • Neoplasm Invasiveness
  • Serrate-Jagged Proteins
  • Tumor Cells, Cultured

Substances

  • Calcium-Binding Proteins
  • Intercellular Signaling Peptides and Proteins
  • JAG1 protein, human
  • Jagged-1 Protein
  • MIRN186 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Serrate-Jagged Proteins