MiR-17-92 and miR-221/222 cluster members target KIT and ETV1 in human gastrointestinal stromal tumours

Autor: Erik A.C. Wiemer, Patrick Schöffski, Antonius W. M. Boersma, Stefan Sleijfer, Caroline M.M. Gits, Ron H.J. Mathijssen, Moniek B E Jonkers, W F J van IJcken, Agnieszka Wozniak, Piotr Rutkowski, P F van Kuijk, Raf Sciot, Jaap Verweij, Takahiro Taguchi, Maria Debiec-Rychter
Přispěvatelé: Medical Oncology, Cell biology
Rok vydání: 2013
Předmět:
Zdroj: British Journal of Cancer, 109(6), 1625-1635. Nature Publishing Group
British Journal of Cancer
ISSN: 1532-1827
0007-0920
Popis: BACKGROUND: Gastrointestinal stromal tumours (GIST) are characterised by high expression of KIT and ETV1, which cooperate in GIST oncogenesis. Our aim was to identify microRNAs that are deregulated in GIST, have a role in GIST pathogenesis, and could potentially be used as therapeutic tool.METHODS: Differentially expressed microRNAs between primary GIST (n=50) and gastrointestinal leiomyosarcomas (GI-LMS, n=10) were determined using microarrays. Selected microRNA mimics were transfected into GIST-882 and GIST-T1 cell lines to study the effects of microRNA overexpression on GIST cells. Luciferase reporter assays were used to establish regulation of target genes by selected microRNAs.RESULTS: MiR-17-92 and miR-221/222 cluster members were significantly (PCONCLUSION: MicroRNAs that may have an essential role in GIST pathogenesis were identified, in particular miR-17/20a/222 that target KIT and ETV1. Delivering these microRNAs therapeutically could hold great potential for GIST management, especially in imatinib-resistant disease.
Databáze: OpenAIRE