PMID- 22409234
OWN - NLM
STAT- MEDLINE
DCOM- 20120726
LR  - 20160511
IS  - 2159-3345 (Electronic)
IS  - 2159-3337 (Linking)
VI  - 22
IP  - 2
DP  - 2012 Apr
TI  - The regulatory network menin-microRNA 26a as a possible target for RNA-based 
      therapy of bone diseases.
PG  - 103-8
LID - 10.1089/nat.2012.0344 [doi]
AB  - 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.
FAU - Luzi, Ettore
AU  - Luzi E
AD  - Metabolic Bone Unit, Department of Internal Medicine, University of Florence, 
      Florence, Italy.
FAU - Marini, Francesca
AU  - Marini F
FAU - Tognarini, Isabella
AU  - Tognarini I
FAU - Galli, Gianna
AU  - Galli G
FAU - Falchetti, Alberto
AU  - Falchetti A
FAU - Brandi, Maria Luisa
AU  - Brandi ML
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120312
PL  - United States
TA  - Nucleic Acid Ther
JT  - Nucleic acid therapeutics
JID - 101562758
RN  - 0 (3' Untranslated Regions)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (MEN1 protein, human)
RN  - 0 (MIRN26A microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (SMAD1 protein, human)
RN  - 0 (Smad1 Protein)
RN  - EC 1.13.12.5 (Luciferases, Renilla)
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
SB  - IM
MH  - 3' Untranslated Regions/genetics
MH  - Adipose Tissue/cytology
MH  - Alkaline Phosphatase/metabolism
MH  - Antigens, Differentiation/genetics/metabolism
MH  - Bone Diseases/therapy
MH  - Cell Differentiation/genetics
MH  - Chromatin Immunoprecipitation
MH  - Gene Expression
MH  - *Gene Regulatory Networks
MH  - Genes, Reporter
MH  - Humans
MH  - Luciferases, Renilla/biosynthesis/genetics
MH  - MicroRNAs/*genetics/metabolism
MH  - Osteoblasts/cytology
MH  - Protein Binding
MH  - Proto-Oncogene Proteins/*genetics/metabolism
MH  - RNA Interference
MH  - Smad1 Protein/genetics/metabolism
MH  - Stem Cells/*physiology
EDAT- 2012/03/14 06:00
MHDA- 2012/07/27 06:00
CRDT- 2012/03/14 06:00
PHST- 2012/03/14 06:00 [entrez]
PHST- 2012/03/14 06:00 [pubmed]
PHST- 2012/07/27 06:00 [medline]
AID - 10.1089/nat.2012.0344 [doi]
PST - ppublish
SO  - Nucleic Acid Ther. 2012 Apr;22(2):103-8. doi: 10.1089/nat.2012.0344. Epub 2012 
      Mar 12.