TY - JOUR
T1 - Fascin-1 overexpression and miR-133b downregulation in the progression of gastrointestinal stromal tumor
AU - Yamamoto, Hidetaka
AU - Kohashi, Kenichi
AU - Fujita, Aya
AU - Oda, Yoshinao
N1 - Funding Information:
This study was supported in part by Grants-in-Aid for Scientific Research from the Japan Society of the Promotion of Science, Tokyo, Japan (Grant number 22790346; H Yamamoto).
Funding Information:
We appreciate the technical support from the Research Support Center, Graduate School of Medical Sciences, Kyushu University. We also thank Ms Naomi Tateishi, Kyushu University, and Mr Satoshi Kondou, Toray, for their great technical assistance. The English used in the manuscript was improved by KN International (http://www.kninter.com/).
Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/4
Y1 - 2013/4
N2 - MicroRNAs (miRNAs) are small, non-coding RNAs that are up-or downregulated in several types of cancer, and have an important role in the tumorigenesis and progression. To better understand the role of aberrantly expressed miRNAs and their target genes affecting the biology of gastrointestinal stromal tumor (GIST), we performed miRNA array in 19 cases of GIST, and found that several miRNAs, including miR-133b, were downregulated in high-grade GISTs. Subsequently, quantitative real-time reverse transcription-PCR revealed that fascin-1 mRNA was upregulated in accordance with miR-133b downregulation in high-grade GIST; this result was consistent with a previous report showing that fascin-1 might be a direct target of miR-133b. We then examined the fascin-1 protein expression by immunohistochemical staining in 147 cases of GIST, and found that fascin-1 overexpression was significantly correlated with shorter disease-free survival time and several aggressive pathological factors, including tumor size, mitotic counts, risk grade, blood vessel invasion and mucosal ulceration. Our results suggest that downregulation of miR-133b and overexpression of fascin-1 may have an important role in the progression of GIST, and that fascin-1 may be a useful biomarker to predict the aggressive behavior.
AB - MicroRNAs (miRNAs) are small, non-coding RNAs that are up-or downregulated in several types of cancer, and have an important role in the tumorigenesis and progression. To better understand the role of aberrantly expressed miRNAs and their target genes affecting the biology of gastrointestinal stromal tumor (GIST), we performed miRNA array in 19 cases of GIST, and found that several miRNAs, including miR-133b, were downregulated in high-grade GISTs. Subsequently, quantitative real-time reverse transcription-PCR revealed that fascin-1 mRNA was upregulated in accordance with miR-133b downregulation in high-grade GIST; this result was consistent with a previous report showing that fascin-1 might be a direct target of miR-133b. We then examined the fascin-1 protein expression by immunohistochemical staining in 147 cases of GIST, and found that fascin-1 overexpression was significantly correlated with shorter disease-free survival time and several aggressive pathological factors, including tumor size, mitotic counts, risk grade, blood vessel invasion and mucosal ulceration. Our results suggest that downregulation of miR-133b and overexpression of fascin-1 may have an important role in the progression of GIST, and that fascin-1 may be a useful biomarker to predict the aggressive behavior.
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U2 - 10.1038/modpathol.2012.198
DO - 10.1038/modpathol.2012.198
M3 - Article
C2 - 23196799
AN - SCOPUS:84876498002
VL - 26
SP - 563
EP - 571
JO - Modern Pathology
JF - Modern Pathology
SN - 0893-3952
IS - 4
ER -
