PMID- 20484036
OWN - NLM
STAT- MEDLINE
DCOM- 20100617
LR  - 20230523
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 70
IP  - 11
DP  - 2010 Jun 1
TI  - Regulation of insulin-like growth factor-mammalian target of rapamycin signaling 
      by microRNA in childhood adrenocortical tumors.
PG  - 4666-75
LID - 10.1158/0008-5472.CAN-09-3970 [doi]
AB  - MicroRNAs (miRNAs) act at the posttranscriptional level to control gene 
      expression in virtually every biological process, including oncogenesis. Here, we 
      report the identification of a set of miRNAs that are differentially regulated in 
      childhood adrenocortical tumors (ACT), including miR-99a and miR-100. Functional 
      analysis of these miRNAs in ACT cell lines showed that they coordinately regulate 
      expression of the insulin-like growth factor-mammalian target of rapamycin 
      (mTOR)-raptor signaling pathway through binding sites in their 3'-untranslated 
      regions. In these cells, the active Ser(2448)-phosphorylated form of mTOR is 
      present only in mitotic cells in association with the mitotic spindle and midbody 
      in the G(2)-M phases of the cell cycle. Pharmacologic inhibition of mTOR 
      signaling by everolimus greatly reduces tumor cell growth in vitro and in vivo. 
      Our results reveal a novel mechanism of regulation of mTOR signaling by miRNAs, 
      and they lay the groundwork for clinical evaluation of drugs inhibiting the mTOR 
      pathway for treatment of adrenocortical cancer.
CI  - Copyright 2010 AACR.
FAU - Doghman, Mabrouka
AU  - Doghman M
AD  - Institut de Pharmacologie Moleculaire et Cellulaire, 660 route des Lucioles, 
      06560 Valbonne, France.
FAU - El Wakil, Abeer
AU  - El Wakil A
FAU - Cardinaud, Bruno
AU  - Cardinaud B
FAU - Thomas, Emilie
AU  - Thomas E
FAU - Wang, Jinling
AU  - Wang J
FAU - Zhao, Wei
AU  - Zhao W
FAU - Peralta-Del Valle, Maria Helena C
AU  - Peralta-Del Valle MH
FAU - Figueiredo, Bonald C
AU  - Figueiredo BC
FAU - Zambetti, Gerard P
AU  - Zambetti GP
FAU - Lalli, Enzo
AU  - Lalli E
LA  - eng
GR  - R01 GM083159/GM/NIGMS NIH HHS/United States
GR  - P01 CA071907/CA/NCI NIH HHS/United States
GR  - P01 CA071907-060006/CA/NCI NIH HHS/United States
GR  - GM083159/GM/NIGMS NIH HHS/United States
GR  - CA21765/CA/NCI NIH HHS/United States
GR  - P30 CA021765/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100518
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (MicroRNAs)
RN  - 0 (Somatomedins)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adrenal Cortex Neoplasms/genetics/*metabolism/pathology
MH  - Adrenocortical Adenoma/genetics/*metabolism/pathology
MH  - Adrenocortical Carcinoma/genetics/*metabolism/pathology
MH  - Animals
MH  - Cell Growth Processes/physiology
MH  - Everolimus
MH  - Female
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/antagonists & 
      inhibitors/*metabolism
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - MicroRNAs/genetics/*metabolism
MH  - Protein Serine-Threonine Kinases/antagonists & inhibitors/*metabolism
MH  - Sirolimus/analogs & derivatives/pharmacology
MH  - Somatomedins/*metabolism
MH  - TOR Serine-Threonine Kinases
MH  - Transplantation, Heterologous
PMC - PMC2880211
MID - NIHMS192514
COIS- Conflict of interest: None declared.
EDAT- 2010/05/21 06:00
MHDA- 2010/06/18 06:00
PMCR- 2011/06/01
CRDT- 2010/05/21 06:00
PHST- 2010/05/21 06:00 [entrez]
PHST- 2010/05/21 06:00 [pubmed]
PHST- 2010/06/18 06:00 [medline]
PHST- 2011/06/01 00:00 [pmc-release]
AID - 0008-5472.CAN-09-3970 [pii]
AID - 10.1158/0008-5472.CAN-09-3970 [doi]
PST - ppublish
SO  - Cancer Res. 2010 Jun 1;70(11):4666-75. doi: 10.1158/0008-5472.CAN-09-3970. Epub 
      2010 May 18.