PMID- 22983984
OWN - NLM
STAT- MEDLINE
DCOM- 20130308
LR  - 20220408
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Linking)
VI  - 33
IP  - 12
DP  - 2012 Dec
TI  - Downregulation of miR-144 is associated with colorectal cancer progression via 
      activation of mTOR signaling pathway.
PG  - 2391-7
LID - 10.1093/carcin/bgs288 [doi]
AB  - The mammalian target of rapamycin (mTOR) is a downstream integrator of essential 
      pathways. mTOR signaling is frequently dysregulated in a variety of human 
      cancers, and in silico analysis has revealed two miR-144 binding sites in the 
      mTOR 3' untranslated region. We investigated the clinicopathologic magnitude of 
      the mTOR pathway regulating microRNA, miR-144 in colorectal cancer (CRC) cases. 
      The regulation of mTOR by miR-144 was examined with inhibitor miR-144-transfected 
      cells. We also investigated changes in sensitivity to the mTOR inhibitor, 
      rapamycin, in inhibitor miR-144-transfected cells. Quantitative RT-PCR was used 
      to evaluate the clinicopathologic significance of miR-144 expression in 137 CRC. 
      Furthermore, we assessed the correlation between CRC prognosis and the expression 
      of 16 genes in the Akt/mTOR pathway. In vitro assays showed that mTOR is a direct 
      target of miR-144, and downregulation of miR-144 facilitated proliferation of CRC 
      cell line, HT29. In addition, the viability of HT29 cells with downregulated 
      miR-144 expression was significantly reduced with rapamycin treatment. Low 
      expression levels of miR-144 were associated with enhanced malignant potential 
      such as venous invasion (P = 0.0013), liver metastasis (P = 0.08), liver 
      recurrence (P = 0.0058) and poor prognosis (P = 0.0041). Multivariate analysis 
      indicated that low miR-144 expression was an independent prognostic factor for 
      survival. Among many genes consisting of the mTOR pathway, only high expression 
      of Rictor was associated with poor prognosis of CRC. miR-144 is a meaningful 
      prognostic marker. Downregulation of miR-144 leads to poor prognosis of CRC 
      patients via activation of the mTOR signaling pathway.
FAU - Iwaya, Takeshi
AU  - Iwaya T
AD  - Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 
      874-0838, Japan. takeiwaya@gmail.com
FAU - Yokobori, Takehiko
AU  - Yokobori T
FAU - Nishida, Naohiro
AU  - Nishida N
FAU - Kogo, Ryunosuke
AU  - Kogo R
FAU - Sudo, Tomoya
AU  - Sudo T
FAU - Tanaka, Fumiaki
AU  - Tanaka F
FAU - Shibata, Kohei
AU  - Shibata K
FAU - Sawada, Genta
AU  - Sawada G
FAU - Takahashi, Yusuke
AU  - Takahashi Y
FAU - Ishibashi, Masahisa
AU  - Ishibashi M
FAU - Wakabayashi, Go
AU  - Wakabayashi G
FAU - Mori, Masaki
AU  - Mori M
FAU - Mimori, Koshi
AU  - Mimori K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120915
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (MIRN144 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Cell Proliferation
MH  - Colorectal Neoplasms/*etiology/mortality/pathology
MH  - Disease Progression
MH  - Down-Regulation
MH  - HT29 Cells
MH  - Humans
MH  - MicroRNAs/antagonists & inhibitors/*physiology
MH  - Signal Transduction/*physiology
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/*physiology
EDAT- 2012/09/18 06:00
MHDA- 2013/03/09 06:00
CRDT- 2012/09/18 06:00
PHST- 2012/09/18 06:00 [entrez]
PHST- 2012/09/18 06:00 [pubmed]
PHST- 2013/03/09 06:00 [medline]
AID - bgs288 [pii]
AID - 10.1093/carcin/bgs288 [doi]
PST - ppublish
SO  - Carcinogenesis. 2012 Dec;33(12):2391-7. doi: 10.1093/carcin/bgs288. Epub 2012 Sep 
      15.