MiRNA profiling of gastrointestinal stromal tumors by next-generation sequencing
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Ugne Gyvyte1,*, Simonas Juzenas1,*, Violeta Salteniene1, Juozas Kupcinskas1,2, Lina Poskiene3, Laimutis Kucinskas1, Sonata Jarmalaite4,5, Kristina Stuopelyte4,5, Ruta Steponaitiene1, Georg Hemmrich-Stanisak6, Matthias Hübenthal6, Alexander Link7, Sabine Franke8, Andre Franke6, Dalia Pangonyte3, Vaiva Lesauskaite9, Limas Kupcinskas1,2,#, Jurgita Skieceviciene1,#
1Institute for Digestive Research, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania
2Department of Gastroenterology, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania
3Department of Pathological Anatomy, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania
4Division of Human Genome Research Centre, Institute of Biosciences, Life Sciences Center, Vilnius University, Vilnius, Lithuania
5National Cancer Institute, Vilnius, Lithuania
6Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Kiel, Germany
7Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital Magdeburg, Magdeburg, Germany
8Institute of Pathology, Otto-von-Guericke University, Magdeburg, Germany
9Institute of Cardiology, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania
*These authors contributed equally to this work
#These authors jointly supervised this work
Jurgita Skieceviciene, email: [email protected]
Keywords: GIST, microRNA, microRNA profiling, small RNA-seq
Received: May 24, 2016 Accepted: March 12, 2017 Published: March 29, 2017
Deregulation of miRNAs has been observed virtually in all major types of cancer, whereas the miRNA signature in GIST is not well characterized yet. In this study the first high-throughput miRNA profiling of 15 paired GIST and adjacent normal tissue samples was performed using small RNA-seq approach and differentially expressed miRNAs as well as isomiRNAs were defined. Highly significantly deregulated miRNAs were selected for validation by Taq-Man low-density array in replication group of 40 paired samples. Validated miRNAs were further subjected to enrichment analysis, which revealed significantly enriched KEGG pathways in the main GIST associated pathways. Further, we used an integrated analysis of miRNA-mRNA correlations for KIT and PDGFRA target genes and found a significant correlation between all of the enriched miRNAs and their target gene KIT. Results of the phenotype analysis showed miR-509-3p to be up-regulated in epithelioid and mixed cell types compared to spindle type, whereas miR-215-5p showed negative correlation with risk grade of GIST. These data reveal a detailed miRNA profile of GIST and highlight new candidates that may be important in the development of malignant disease.
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