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 |
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Přispěvatelé: | Medical Oncology, Cell biology |
Rok vydání: | 2013 |
Předmět: |
Adult
Male Cancer Research Pathology medicine.medical_specialty Carcinogenesis Gastrointestinal Stromal Tumors Apoptosis Cell Growth Processes Biology Transfection medicine.disease_cause ETV1 microRNA medicine Humans Molecular Diagnostics neoplasms Aged Aged 80 and over miR-17 GiST Cell growth KIT Middle Aged miR-222 digestive system diseases DNA-Binding Proteins MicroRNAs Proto-Oncogene Proteins c-kit Oncology Cell culture Multigene Family Cancer research Female miR-20a Transcription Factors GIST |
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 |
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