PMID- 23864387
OWN - NLM
STAT- MEDLINE
DCOM- 20140409
LR  - 20211021
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 34
IP  - 12
DP  - 2013 Dec
TI  - Insulin-like growth factor-I receptor is suppressed through transcriptional 
      repression and mRNA destabilization by a novel energy restriction-mimetic agent.
PG  - 2694-705
LID - 10.1093/carcin/bgt251 [doi]
AB  - Insulin-like growth factor-I receptor (IGF-IR) represents one of the major 
      targets by which dietary or chemically induced energy restriction mediates 
      chemopreventive effects in animal tumor models. However, the mechanism underlying 
      this cellular response remains unclear. In the course of investigating the 
      suppressive effect of the energy restriction-mimetic agent CG-5 on IGF-IR 
      expression in prostate cancer cells, we identified a novel posttranscriptional 
      mechanism by which the RNA-binding protein human antigen R (HuR) regulates IGF-IR 
      expression through messenger RNA (mRNA) stabilization. Previously, we 
      demonstrated that Sp1 and HuR proteins were concomitantly targeted for 
      ubiquitin-dependent degradation by beta-transducin repeat-containing protein in 
      response to CG-5. Although this loss of Sp1 expression contributed to 
      CG-5-mediated IGF-IR downregulation, enforced specific protein 1 (Sp1) expression 
      could only partially protect cells from the drug effect. The small interfering 
      RNA-mediated silencing of HuR suppressed IGF-IR expression by reducing mRNA 
      stability, whereas ectopic HuR expression increased IGF-IR mRNA stability and 
      protein expression and, when coexpressed with Sp1, blocked CG-5-mediated IGF-IR 
      ablation. RNA pull-down and immunoprecipitation analyses indicated that HuR 
      selectively bound to the distal region of the IGF-IR 3' untranslated region 
      (UTR), whereas no interaction with the 5'UTR was noted. Evaluation of a series of 
      truncated HuR mutants revealed that the RNA recognition motifs (RRM2 and RRM3) 
      were involved in IGF-IR 3'UTR binding and the consequent increase in IGF-IR mRNA 
      stability. Although these data contrast with a previous report that HuR acted as 
      a translation repressor of IGF-IR mRNA through 5'UTR binding, our finding is 
      consistent with the reported oncogenic role of HuR in conferring stability to 
      target mRNAs encoding tumor-promoting proteins.
FAU - Chu, Po-Chen
AU  - Chu PC
AD  - Division of Medicinal Chemistry, College of Pharmacy and Comprehensive Cancer 
      Center, The Ohio State University, Columbus, OH 43221, USA and.
FAU - Kulp, Samuel K
AU  - Kulp SK
FAU - Chen, Ching-Shih
AU  - Chen CS
LA  - eng
GR  - P30 CA016058/CA/NCI NIH HHS/United States
GR  - R01 CA112250/CA/NCI NIH HHS/United States
GR  - R01CA112250/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Retracted Publication
DEP - 20130716
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (3' Untranslated Regions)
RN  - 0 (5' Untranslated Regions)
RN  - 0 (ELAV Proteins)
RN  - 0 (Immunoglobulins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (SP1 antigen)
RN  - EC 1.17.4.- (ribonucleotide reductase M2)
RN  - EC 1.17.4.1 (Ribonucleoside Diphosphate Reductase)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
SB  - IM
EIN - Carcinogenesis. 2017 Jan;38(1):105-106. PMID: 28064180
RIN - Carcinogenesis. 2019 Apr 29;40(2):e14. PMID: 31034564
MH  - 3' Untranslated Regions/genetics
MH  - 5' Untranslated Regions/genetics
MH  - Cell Line, Tumor
MH  - Down-Regulation/genetics
MH  - ELAV Proteins/genetics
MH  - Glycolysis/genetics
MH  - Humans
MH  - Immunoglobulins/genetics
MH  - Male
MH  - Prostatic Neoplasms/genetics
MH  - RNA Processing, Post-Transcriptional/genetics
MH  - RNA Stability/genetics
MH  - RNA, Messenger/*genetics
MH  - RNA-Binding Proteins/genetics
MH  - Receptor, IGF Type 1/*genetics
MH  - Ribonucleoside Diphosphate Reductase/genetics
MH  - Transcription, Genetic/*genetics
PMC - PMC3845891
EDAT- 2013/07/19 06:00
MHDA- 2014/04/10 06:00
PMCR- 2014/12/01
CRDT- 2013/07/19 06:00
PHST- 2013/07/19 06:00 [entrez]
PHST- 2013/07/19 06:00 [pubmed]
PHST- 2014/04/10 06:00 [medline]
PHST- 2014/12/01 00:00 [pmc-release]
AID - bgt251 [pii]
AID - 10.1093/carcin/bgt251 [doi]
PST - ppublish
SO  - Carcinogenesis. 2013 Dec;34(12):2694-705. doi: 10.1093/carcin/bgt251. Epub 2013 
      Jul 16.