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.
Keywords: KIT, PDGFRA, GIST, MicroRNA, RNA therapy, mesenchymal tumor, mutations, Imatinib, cell proliferation, tumorigenesis
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