title: Fascin-1 overexpression and miR-133b downregulation in the progression of gastrointestinal stromal tumor.
abstract: 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.
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan. hidetaka@surgpath.med.kyushu-u.ac.jp
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kohashi
authors.forename: Aya
authors.initials: A
authors.lastname: Fujita
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis*; D018450:Disease Progression; D018572:Disease-Free Survival; D015536:Down-Regulation; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000235:genetics*; D008840:Microfilament Proteins / Q000096:biosynthesis*; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019089:Stem Cell Factor / Q000235:genetics; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C502658:FSCN1 protein, human; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D008840:Microfilament Proteins; D019089:Stem Cell Factor; D020796:Receptor, Platelet-Derived Growth Factor alpha