Integrated analysis of circular RNA-associated ceRNA network in pancreatic ductal adenocarcinoma.

Circular RNAs (circRNAs) have displayed dysregulated expression in several types of cancer. However, the functions of the majority of circRNAs in pancreatic ductal adenocarcinoma (PDAC) remain unknown. The present study aimed to investigate the expression, functions and molecular mechanisms of circRNAs in PDAC. The circRNAs, mRNAs and the microRNA (miRNAs) expression profiles were obtained from three Gene Expression Omnibus microarray datasets, and a circRNA-miRNA-mRNA and circRNA-miRNA-hubgene network was established. The interactions between proteins were analyzed using the Search Tool for the Retrieval of Interacting Genes/Proteins database, and hubgenes were identified using the MCODE plugin. A total of eight differentially expressed circRNAs (DEcircRNAs), 44 differentially expressed miRNAs (DEmiRNAs), and 2,052 differentially expressed mRNAs (DEmRNAs) were identified. The present study successfully constructed a circRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network based on four circRNAs, six miRNAs and 111 mRNAs in PDAC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathways analyses indicated that DEmRNAs may participate in the pathogenesis and progression of PDAC. The protein-protein interaction network and module analysis identified six hubgenes (THBS1, FN1, TIMP3, TGFB2, ITGA1 and ITGA3). Furthermore, the circRNA-miRNA-hubgene regulatory modules were constructed based on the three DEcircRNAs, one DEmiRNAs and five DEmRNAs. In conclusion, the results of the present study improve the current understanding of the pathogenesis of PDAC.