PMID- 22761894
OWN - NLM
STAT- MEDLINE
DCOM- 20130104
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 6
DP  - 2012
TI  - The negative feedback-loop between the oncomir Mir-24-1 and menin modulates the 
      Men1 tumorigenesis by mimicking the "Knudson's second hit".
PG  - e39767
LID - 10.1371/journal.pone.0039767 [doi]
LID - e39767
AB  - Multiple endocrine neoplasia type 1 (MEN1) syndrome is a rare hereditary cancer 
      disorder characterized by tumors of the parathyroids, of the neuroendocrine 
      cells, of the gastro-entero-pancreatic tract, of the anterior pituitary, and by 
      non-endocrine neoplasms and lesions. MEN1 gene, a tumor suppressor gene, encodes 
      menin protein. Loss of heterozygosity at 11q13 is typical of MEN1 tumors, in 
      agreement with the Knudson's two-hit hypothesis. In silico analysis with Target 
      Scan, Miranda and Pictar-Vert softwares for the prediction of miRNA targets 
      indicated miR-24-1 as capable to bind to the 3'UTR of MEN1 mRNA. We investigated 
      this possibility by analysis of miR-24-1 expression profiles in parathyroid 
      adenomatous tissues from MEN1 gene mutation carriers, in their sporadic non-MEN1 
      counterparts, and in normal parathyroid tissue. Interestingly, the MEN1 
      tumorigenesis seems to be under the control of a "negative feedback loop" between 
      miR-24-1 and menin protein, that mimics the second hit of Knudson's hypothesis 
      and that could buffer the effect of the stochastic factors that contribute to the 
      onset and progression of this disease. Our data show an alternative way to MEN1 
      tumorigenesis and, probably, to the "two-hit dogma". The functional significance 
      of this regulatory mechanism in MEN1 tumorigenesis is also the basis for opening 
      future developments of RNA antagomir(s)-based strategies in the in vivo control 
      of tumorigenesis in MEN1 carriers.
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 - Giusti, Francesca
AU  - Giusti F
FAU - Galli, Gianna
AU  - Galli G
FAU - Cavalli, Loredana
AU  - Cavalli L
FAU - Brandi, Maria Luisa
AU  - Brandi ML
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120627
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (3' Untranslated Regions)
RN  - 0 (MEN1 protein, human)
RN  - 0 (MIRN24 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - 3' Untranslated Regions
MH  - Adenoma/genetics/metabolism
MH  - Cell Transformation, Neoplastic
MH  - *Feedback, Physiological
MH  - Gene Expression Profiling
MH  - Loss of Heterozygosity
MH  - MicroRNAs/*physiology
MH  - Parathyroid Neoplasms/genetics/metabolism
MH  - Proto-Oncogene Proteins/genetics/*physiology
PMC - PMC3384621
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/07/05 06:00
MHDA- 2013/01/05 06:00
PMCR- 2012/06/27
CRDT- 2012/07/05 06:00
PHST- 2012/04/04 00:00 [received]
PHST- 2012/05/30 00:00 [accepted]
PHST- 2012/07/05 06:00 [entrez]
PHST- 2012/07/05 06:00 [pubmed]
PHST- 2013/01/05 06:00 [medline]
PHST- 2012/06/27 00:00 [pmc-release]
AID - PONE-D-12-11166 [pii]
AID - 10.1371/journal.pone.0039767 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(6):e39767. doi: 10.1371/journal.pone.0039767. Epub 2012 Jun 27.