PMID- 25594065
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150116
LR  - 20201001
IS  - 2331-4737 (Print)
IS  - 2331-4737 (Electronic)
IS  - 2331-4737 (Linking)
VI  - 1
IP  - 9
DP  - 2014
TI  - Menin-mediated regulation of miRNA biogenesis uncovers the IRS2 pathway as a 
      target for regulating pancreatic beta cells.
PG  - 562-6
AB  - Menin, a protein encoded by the MEN1 gene, is mutated in patients with multiple 
      endocrine neoplasia type 1 (MEN1). Menin acts as a tumor suppressor in endocrine 
      organs while it is also required for transformation of a subgroup of leukemia. 
      The recently solved crystal structure of menin with different binding partners 
      reveals that menin is a key scaffold protein that cross-talks with various 
      partners, including transcription factors, to regulate gene transcription. Our 
      recent findings unravel a previously undiscovered mechanism for menin-mediated 
      control of gene expression via processing of certain microRNA's, thus adding to 
      the plethora of ways in which menin regulates gene expression. By interacting 
      with ARS2, an RNA binding protein, menin facilitates the processing of pri-let 7a 
      and pri-miR155 to pre-let 7a and pre-miR155 respectively. Consistently, excision 
      of the Men1 gene results in upregulation of IRS2, a let-7a target. As IRS2 is 
      known to mediate both insulin signaling and insulin-induced cell proliferation, 
      and let-7a targets include oncogenes like RAS and HMGA2, a deeper understanding 
      of the menin-ARS2 complex in regulating miRNA biogenesis will yield further 
      insights into the pathogenesis of the MEN1 syndrome and other menin-associated 
      malignancies.
FAU - Gurung, Buddha
AU  - Gurung B
AD  - Abramson Family Cancer Research Institute, Department of Cancer Biology, 
      University of Pennsylvania Perelman School of Medicine, 421 Curie Blvd., BRB 
      II/III, Philadelphia, PA-19104, USA.
FAU - Katona, Bryson W
AU  - Katona BW
AD  - Abramson Family Cancer Research Institute, Department of Cancer Biology, 
      University of Pennsylvania Perelman School of Medicine, 421 Curie Blvd., BRB 
      II/III, Philadelphia, PA-19104, USA ; Division of Gastroenterology, University of 
      Pennsylvania Perelman School of Medicine, 421 Curie Blvd., BRB II/III, 
      Philadelphia, PA-19104, USA.
FAU - Hua, Xianxin
AU  - Hua X
AD  - Abramson Family Cancer Research Institute, Department of Cancer Biology, 
      University of Pennsylvania Perelman School of Medicine, 421 Curie Blvd., BRB 
      II/III, Philadelphia, PA-19104, USA.
LA  - eng
GR  - P30 DK050306/DK/NIDDK NIH HHS/United States
GR  - R01 CA113962/CA/NCI NIH HHS/United States
GR  - R01 DK085121/DK/NIDDK NIH HHS/United States
GR  - T32 DK007066/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20140915
PL  - United States
TA  - Oncoscience
JT  - Oncoscience
JID - 101636666
PMC - PMC4278340
OTO - NOTNLM
OT  - ARS2
OT  - IRS1
OT  - Let7a
OT  - Menin
OT  - beta cell
OT  - miRNA processing
EDAT- 2015/01/17 06:00
MHDA- 2015/01/17 06:01
PMCR- 2014/09/15
CRDT- 2015/01/17 06:00
PHST- 2014/09/04 00:00 [received]
PHST- 2014/09/08 00:00 [accepted]
PHST- 2015/01/17 06:00 [entrez]
PHST- 2015/01/17 06:00 [pubmed]
PHST- 2015/01/17 06:01 [medline]
PHST- 2014/09/15 00:00 [pmc-release]
AID - 79 [pii]
AID - 10.18632/oncoscience.79 [doi]
PST - epublish
SO  - Oncoscience. 2014 Sep 15;1(9):562-6. doi: 10.18632/oncoscience.79. eCollection 
      2014.