PMID- 24855947
OWN - NLM
STAT- MEDLINE
DCOM- 20140723
LR  - 20231213
IS  - 1097-4172 (Electronic)
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 157
IP  - 5
DP  - 2014 May 22
TI  - An essential mesenchymal function for miR-143/145 in intestinal epithelial 
      regeneration.
PG  - 1104-16
LID - S0092-8674(14)00489-9 [pii]
LID - 10.1016/j.cell.2014.03.055 [doi]
AB  - Downregulation of the miR-143/145 microRNA (miRNA) cluster has been repeatedly 
      reported in colon cancer and other epithelial tumors. In addition, overexpression 
      of these miRNAs inhibits tumorigenesis, leading to broad consensus that they 
      function as cell-autonomous epithelial tumor suppressors. We generated mice with 
      deletion of miR-143/145 to investigate the functions of these miRNAs in 
      intestinal physiology and disease in vivo. Although intestinal development 
      proceeded normally in the absence of these miRNAs, epithelial regeneration after 
      injury was dramatically impaired. Surprisingly, we found that miR-143/145 are 
      expressed and function exclusively within the mesenchymal compartment of 
      intestine. Defective epithelial regeneration in miR-143/145-deficient mice 
      resulted from the dysfunction of smooth muscle and myofibroblasts and was 
      associated with derepression of the miR-143 target Igfbp5, which impaired IGF 
      signaling after epithelial injury. These results provide important insights into 
      the regulation of epithelial wound healing and argue against a cell-autonomous 
      tumor suppressor role for miR-143/145 in colon cancer.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Chivukula, Raghu R
AU  - Chivukula RR
AD  - Medical Scientist Training Program, Johns Hopkins University School of Medicine, 
      Baltimore, MD 21205, USA.
FAU - Shi, Guanglu
AU  - Shi G
AD  - Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX 
      75390, USA.
FAU - Acharya, Asha
AU  - Acharya A
AD  - Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX 
      75390, USA.
FAU - Mills, Eric W
AU  - Mills EW
AD  - Medical Scientist Training Program, Johns Hopkins University School of Medicine, 
      Baltimore, MD 21205, USA.
FAU - Zeitels, Lauren R
AU  - Zeitels LR
AD  - Medical Scientist Training Program, Johns Hopkins University School of Medicine, 
      Baltimore, MD 21205, USA.
FAU - Anandam, Joselin L
AU  - Anandam JL
AD  - Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA.
FAU - Abdelnaby, Abier A
AU  - Abdelnaby AA
AD  - Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA.
FAU - Balch, Glen C
AU  - Balch GC
AD  - Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA.
FAU - Mansour, John C
AU  - Mansour JC
AD  - Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA.
FAU - Yopp, Adam C
AU  - Yopp AC
AD  - Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA.
FAU - Maitra, Anirban
AU  - Maitra A
AD  - Sheikh Ahmed Bin Zayed Al Nahyan Center for Pancreatic Cancer Research, UT MD 
      Anderson Cancer Center, Houston, TX 77030, USA.
FAU - Mendell, Joshua T
AU  - Mendell JT
AD  - Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX 
      75390, USA; Harold C. Simmons Cancer Center, UT Southwestern Medical Center, 
      Dallas, TX 75390, USA. Electronic address: joshua.mendell@utsouthwestern.edu.
LA  - eng
SI  - GEO/GSE55651
GR  - T32 GM007814/GM/NIGMS NIH HHS/United States
GR  - T32 GM007309/GM/NIGMS NIH HHS/United States
GR  - R01 CA120185/CA/NCI NIH HHS/United States
GR  - P01 CA134292/CA/NCI NIH HHS/United States
GR  - R01CA120185/CA/NCI NIH HHS/United States
GR  - P30 CA142543/CA/NCI NIH HHS/United States
GR  - 5T32GM007309/GM/NIGMS NIH HHS/United States
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - 5P30CA142543/CA/NCI NIH HHS/United States
GR  - P01CA134292/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Insulin-Like Growth Factor Binding Protein 5)
RN  - 0 (MIRN145a microRNA, mouse)
RN  - 0 (MicroRNAs)
RN  - 0 (MIRN143 microRNA, mouse)
RN  - 0 (Somatomedins)
RN  - 9042-14-2 (Dextran Sulfate)
SB  - IM
CIN - Cell Cycle. 2014;13(19):2988-9. doi: 10.4161/15384101.2014.962852. PMID: 25486556
MH  - Animals
MH  - Colonic Neoplasms/metabolism/pathology
MH  - Dextran Sulfate
MH  - Humans
MH  - Insulin-Like Growth Factor Binding Protein 5/genetics
MH  - Intestinal Mucosa/cytology/*physiology
MH  - Mesoderm/metabolism
MH  - Mice
MH  - MicroRNAs/genetics/*metabolism
MH  - Myofibroblasts/metabolism
MH  - Paracrine Communication
MH  - Regeneration
MH  - Somatomedins/metabolism
PMC - PMC4175516
MID - NIHMS587201
EDAT- 2014/05/27 06:00
MHDA- 2014/07/24 06:00
PMCR- 2015/05/22
CRDT- 2014/05/27 06:00
PHST- 2013/10/01 00:00 [received]
PHST- 2014/01/24 00:00 [revised]
PHST- 2014/03/10 00:00 [accepted]
PHST- 2014/05/27 06:00 [entrez]
PHST- 2014/05/27 06:00 [pubmed]
PHST- 2014/07/24 06:00 [medline]
PHST- 2015/05/22 00:00 [pmc-release]
AID - S0092-8674(14)00489-9 [pii]
AID - 10.1016/j.cell.2014.03.055 [doi]
PST - ppublish
SO  - Cell. 2014 May 22;157(5):1104-16. doi: 10.1016/j.cell.2014.03.055.