Fascin-1 Overexpression and miR-133b Down-Regulation in the Progression of Gastrointestinal Stromal Tumor
Hidetaka Yamamoto, Kenichi Kohashi, Aya Fujita, Yoshinao Oda. Kyushu University, Fukuoka, Japan
Background: MicroRNAs (miRNAs) are small, non-coding RNAs that are up- or down-regulated in several types of cancer, and play an important role in the tumorigenesis and progression. The aim of this study is to better understand the role of aberrantly expressed miRNAs and their target genes affecting the biology of gastrointestinal stromal tumor (GIST).
Design: We performed miRNA array in 19 cases of GIST, and subsequently, we examined the expression levels of miR-133b and fascin-1 by quantitative real-time RT-PCR and immunohistochemical staining.
Results: By miRNA array, several miRNAs, including miR-133b, were down-regulated in high-grade GISTs as compared with low to intermediate-grade GISTs. Subsequently, quantitative real-time RT-PCR revealed that fascin-1 mRNA was up-regulated in accordance with miR-133b down-regulation in high grade GIST; this result was consistent with a previous functional study showing that fascin-1 might be a direct target of miR-133b in carcinoma. 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.
Conclusions: Our results suggest that down-regulation of miR-133b and overexpression of fascin-1 may play an important role in the progression of GIST, and that fascin-1 may be a useful biomarker to predict the aggressive behavior.
Category: Bone & Soft Tissue
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 28, Tuesday Afternoon