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|microRNA-451 regulates macrophage migration inhibitory factor production and proliferation of gastrointestinal cancer cells|
|Authors: ||Bandres, E. (Eva)|
Bitarte, N. (Nerea)
Arias, F. (F.)
Agorreta, J. (Jackeline)
Fortes, P. (Puri)
Aguirre, X. (Xavier)
Zarate, R. (Ruth)
Diaz-Gonzalez, J.A. (Juan Antonio)
Ramirez, N. (Natalia)
Sola, J.J. (Jesús J.)
Jimenez, P. (P.)
Rodriguez, J. (Javier)
Garcia-Foncillas, J. (Jesús)
Migration inhibitory factor production
|Issue Date: ||1-Apr-2009|
|Publisher: ||American Association of Cancer Research|
|Publisher version: ||http://dx.doi.org/10.1158/1078-0432.CCR-08-1818|
|Citation: ||Bandres E, Bitarte N, Arias F, Agorreta J, Fortes P, Agirre X, et al. microRNA-451 regulates macrophage migration inhibitory factor production and proliferation of gastrointestinal cancer cells. Clin Cancer Res 2009 Apr 1;15(7):2281-2290.|
Purpose:microRNAs (miRNA) are small RNAs that function as post-transcriptional regulators of
gene expression.R ecent evidence has shown that somemiRNAs can act as oncogenes or tumor
suppressors.This study was conducted to evaluate the potential association of miRNA expression
with clinical outcome in patients with gastric cancer.
Experimental Design: Expression of 250 human mature miRNAs was measured by real-time
PCR on paraffin-embedded tumor samples of 21patients with gastric cancer stage III uniformly
treated with surgical resection followed by chemoradiation.We identified the miRNAs correlated
with disease-free and overall survival times, and the results were evaluated including 24 other
patients. In vitro cell proliferation and radiosensitivity studies were done to support clinical data.
Results:The results revealed that down-regulation ofmiR-451was associatedwithworse prognosis.
m iR-451was detected by in situ hybridization in epithelial cells and showed decreased
expression in gastric and colorectal cancer versus nontumoral tissues.O verexpression of
miR-451in gastric and colorectal cancer cells reduced cell proliferation and increased sensitivity
to radiotherapy.Microarray and bioinformatic analysis identified the novel oncogene macrophage
migration inhibitory factor (MIF) as a potential target of miR-451.In fact, overexpression of miR-
451down-regulatedmRNA and proteinlevels ofMIF and decreased expression of reporter genes
with MIF target sequences.M oreover, we found a significant inverse correlation between miR-
451and MIF expression in tumoral gastric biopsies.
Conclusions:These findings support the role ofmiR-451as a regulatorof cancerproliferationand
opennewperspectives for thedevelopmentof effectivetherapies forchemoradioresistantcancers
|Permanent link: ||http://hdl.handle.net/10171/16767|
|Appears in Collections:||DA - CIMA - Terapia génica y Hepatología - Vectores - Artículos de revista|
DA - Ciencias - HAP - Artículos de revista
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