Identification of long intergenic non-coding RNAs (lincRNAs) deregulated in gastrointestinal stromal tumors (GISTs).

Ugne Gyvyte, Juozas Kupcinskas, Simonas Juzenas, Ruta Inciuraite, Lina Poskiene, Violeta Salteniene, Alexander Link, Matteo Fassan, Andre Franke, Limas Kupcinskas, Jurgita Skieceviciene
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PloS one
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Long intergenic non-coding RNAs (lincRNAs) are >200 nucleotides long non-coding RNAs, which have been shown to be implicated in carcinogenic processes by interacting with cancer associated genes or other non-coding RNAs. However, their role in development of rare gastrointestinal stromal tumors (GISTs) is barely investigated. Therefore, the aim of this study was to define lincRNAs deregulated in GIST and find new GIST-lincRNA associations. Next-generation sequencing data of paired GIST and adjacent tissue samples from 15 patients were subjected to a web-based lincRNA analysis. Three deregulated lincRNAs (MALAT1, H19 and FENDRR; adjusted p-value < 0.05) were selected for expression validation in a larger group of patients (n = 22) by RT-qPCR method. However, only H19 and FENDRR showed significant upregulation in the validation cohort (adjusted p < 0.05). Further, we performed correlation analyses between expression levels of deregulated lincRNAs and GIST-associated oncogenes or GIST deregulated microRNAs. We found high positive correlations between expression of H19 and known GIST related oncogene ETV1, and between H19 and miR-455-3p. These findings expand the knowledge on lincRNAs deregulated in GIST and may be an important resource for the future studies investigating lincRNAs functionally relevant to GIST carcinogenesis.