The regulatory network menin-microRNA 26a as a possible target for RNA-based therapy of bone diseases

Nucleic Acid Ther. 2012 Apr;22(2):103-8. doi: 10.1089/nat.2012.0344. Epub 2012 Mar 12.


MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression, interplaying with transcription factors in complex regulatory networks. Menin is the product of the MEN1 oncosuppressor gene, responsible for multiple endocrine neoplasia type 1 syndrome. Recent data suggest that menin functions as a general regulator of transcription. Menin expression modulates mesenchymal cell commitment to the myogenic or osteogenic lineages. The microRNA 26a (miR-26a) modulates the expression of SMAD1 protein during the osteoblastic differentiation of human adipose tissue-derived stem cells (hADSCs). We used siRNA silencing against MEN1 mRNA and pre-miR-26 mimics to study the interplay between them and to investigate the interplay between menin and miR-26a as regulators of osteogenic differentiation in the hADSCs. We found that in hADSCs the siRNA-induced silencing of MEN1 mRNA resulted in a down regulation of miR-26a, with a consequent up-regulation of SMAD1 protein. Chromatin immunoprecipitation (ChIP) showed that menin occupies the miR-26-a gene promoter, thus inducing its expression and confirming that menin is a positive regulator of miR-26a. In conclusion, results from this study evidenced, for the first time, a direct interaction between menin transcription factor and miRNA, interaction that seems to play a pivotal role during the hADSCs osteogenesis, thus suggesting a novel target for bone disease RNA-based therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adipose Tissue / cytology
  • Alkaline Phosphatase / metabolism
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / metabolism
  • Bone Diseases / therapy
  • Cell Differentiation / genetics
  • Chromatin Immunoprecipitation
  • Gene Expression
  • Gene Regulatory Networks*
  • Genes, Reporter
  • Humans
  • Luciferases, Renilla / biosynthesis
  • Luciferases, Renilla / genetics
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Osteoblasts / cytology
  • Protein Binding
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • RNA Interference
  • Smad1 Protein / genetics
  • Smad1 Protein / metabolism
  • Stem Cells / physiology*


  • 3' Untranslated Regions
  • Antigens, Differentiation
  • MEN1 protein, human
  • MIRN26A microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins
  • SMAD1 protein, human
  • Smad1 Protein
  • Luciferases, Renilla
  • Alkaline Phosphatase