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.

A comprehensive, cell specific microRNA catalogue of human peripheral blood

“…Within our dataset, we identified sequence variations in 69.0% of detected miRNAs. As already indicated by previous studies in various human tissues, 3′-end modifications were the predominant category ( 10 , 13 , 59 – 61 ).…”

Molecular characterization and pathogenesis of gastrointestinal stromal tumor

“…Moreover, analysis using next generation sequencing identified a series of miRNAs differentially expressed in GISTs. These include miR-509-3p and miR-215-5p, expression of which is associated with cell type and risk grade (133). Another study showed that miR-133b is downregulated and its putative target gene, fascin-1, is overexpressed in high-risk GISTs (134).…”

Small Molecules in Rare Tumors: Emerging Role of MicroRNAs in GIST

“…Kelly et al have shown that miRNA profiles segregate pediatric and adult GIST tumors [ 33 ] indicating that underlying pathophysiological molecular pathways might be differently affected at different ages of disease development. The only study that used high-throughput miRNA profiling of 15 paired GIST and adjacent normal tissue samples was performed using small RNA-seq approach and overall analyzed 1672 known miRNAs [ 47 ]. This study found miR-509 up-regulation in epithelioid and mixed cell types as compared to spindle type, while miR-215 showed negative correlation with risk grade of GIST.…”