title: MiRNA profiling of gastrointestinal stromal tumors by next-generation sequencing.
abstract: 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.
authors.affiliation: Institute for Digestive Research, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Ugne
authors.initials: U
authors.lastname: Gyvyte
authors.affiliation: Institute for Digestive Research, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Simonas
authors.initials: S
authors.lastname: Juzenas
authors.affiliation: Institute for Digestive Research, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Violeta
authors.initials: V
authors.lastname: Salteniene
authors.affiliation: Institute for Digestive Research, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania.|Department of Gastroenterology, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Juozas
authors.initials: J
authors.lastname: Kupcinskas
authors.affiliation: Department of Pathological Anatomy, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Lina
authors.initials: L
authors.lastname: Poskiene
authors.affiliation: Institute for Digestive Research, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Laimutis
authors.initials: L
authors.lastname: Kucinskas
authors.affiliation: Division of Human Genome Research Centre, Institute of Biosciences, Life Sciences Center, Vilnius University, Vilnius, Lithuania.|National Cancer Institute, Vilnius, Lithuania.
authors.forename: Sonata
authors.initials: S
authors.lastname: Jarmalaite
authors.affiliation: Division of Human Genome Research Centre, Institute of Biosciences, Life Sciences Center, Vilnius University, Vilnius, Lithuania.|National Cancer Institute, Vilnius, Lithuania.
authors.forename: Kristina
authors.initials: K
authors.lastname: Stuopelyte
authors.affiliation: Institute for Digestive Research, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Ruta
authors.initials: R
authors.lastname: Steponaitiene
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Kiel, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Hemmrich-Stanisak
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Kiel, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hübenthal
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital Magdeburg, Magdeburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Link
authors.affiliation: Institute of Pathology, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Franke
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Kiel, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.affiliation: Department of Pathological Anatomy, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Dalia
authors.initials: D
authors.lastname: Pangonyte
authors.affiliation: Institute of Cardiology, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Vaiva
authors.initials: V
authors.lastname: Lesauskaite
authors.affiliation: Institute for Digestive Research, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania.|Department of Gastroenterology, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Limas
authors.initials: L
authors.lastname: Kupcinskas
authors.affiliation: Institute for Digestive Research, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Jurgita
authors.initials: J
authors.lastname: Skieceviciene
mesh_terms: D000368:Aged; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D059467:Transcriptome
chemical_list: D035683:MicroRNAs; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha
keywords: GIST; microRNA; microRNA profiling; small RNA-seq