Analysis of potential Circular RNAs in regulating imatinib resistance of Gastrointestinal stromal tumor

Abstract

Introduction: Recent studies have found that circular RNA is an abundant RNA species that belongs to part of the competing endogenous RNA network(ceRNA), which was proven to play an important role in the development, diagnosis and progress of diseases. However, the function of circRNAs in imatinib resistance in Gastrointestinal stromal tumor (GIST) are poorly understood so for. The present study aimed to screen and predict the potential circRNAs in imatinib resistance of GIST using microarray analysis. Methods: We determined the expression of circular RNAs in paired normal gastric tissues(N), primary GIST (gastrointestinal stromal tumor) tissues (YC) and imatinib mesylate secondary resistance GIST tissues(C) with microarray and predicted 8677 dysregulated circular RNAs. Results: Compared with the YC group, we identified 15 circRNAs that were up-regulated and 8 circRNAs that were down-regulated in the C group. Gene ontology (GO)and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that these host linear transcripts that differentially express circular RNAs are involved in many key biological pathways, predicting the potential tumor-genesis and drug resistance mechanismrelated to HIF-1 pathway, later we draw the cirRNA-miRNA-mRNA network involved in the HIF-1 pathway and found several dysregulated circRNAs and the relationship between circRNA-miRNAs-mRNA, such as circRNA_06551, circRNA_14668, circRNA_04497, circRNA_08683, circRNA_09923(Green, down-regulation) and circRNA_23636, circRNA_15734(Red, up-regulation). Conclusion: Taken together, we identified a panel of dysregulated circRNAs that may be potential biomarkers even therapy relevant to the GIST, especially imatinib secondary resistance GIST.