Gene interactions and pathways from curated databases and text-mining
Carcinogenesis 2012, PMID: 22983984

Downregulation of miR-144 is associated with colorectal cancer progression via activation of mTOR signaling pathway.

Iwaya, Takeshi; Yokobori, Takehiko; Nishida, Naohiro; Kogo, Ryunosuke; Sudo, Tomoya; Tanaka, Fumiaki; Shibata, Kohei; Sawada, Genta; Takahashi, Yusuke; Ishibashi, Masahisa; Wakabayashi, Go; Mori, Masaki; Mimori, Koshi

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.

Diseases/Pathways annotated by Medline MESH: Colorectal Neoplasms, Disease Progression
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Text Mining Data

mTOR — miR-144: " The regulation of mTOR by miR-144 was examined with inhibitor miR-144 transfected cells "

Manually curated Databases

No curated data.