title: MicroRNA involvement in gastrointestinal stromal tumor tumorigenesis.
abstract: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. The molecular mechanism of GIST formation is among the best characterized of all human tumors. Activating mutations of the c-Kit-kinase (KIT), a member of the receptor tyrosine kinase III family, are present in 80% of GISTs. Gain-of-function mutations of platelet-derived growth factor receptor A (PDGFRA), a member of the same kinase family, are present in 35% of GISTs that lack KIT mutations. These mutations induce the overexpression and autophosphorylation of KIT and PDGFRA, and result in the activation of downstream signaling pathways. Imatinib, a KIT receptor inhibitor, was developed to treat GIST patients by inactivating signaling pathways. However, some GISTs, especially cases with mutations in exon 13 and 17 of KIT, are resistant to imatinib treatment. Therefore, another approach is needed to develop drugs for GIST treatment. Data also support dysregulation of microRNAs in the progression of many types of cancers. Studies demonstrate that microRNAs directly regulate KIT expression levels in GISTs, and inhibit GIST cell proliferation. This review summarizes the characteristics of GISTs, their molecular and clinical implications, the role of microRNAs in GIST tumorigenesis, and their possible therapeutic potential.
authors.affiliation: Brain Korea 21 Projects for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Won Kyu
authors.initials: WK
authors.lastname: Kim
authors.forename: Han-Kwang
authors.initials: HK
authors.lastname: Yang
authors.forename: Hoguen
authors.initials: H
authors.lastname: Kim
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002869:Chromosome Aberrations; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D015870:Gene Expression; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*
chemical_list: D035683:MicroRNAs