Integrative microRNA-mRNA and protein-protein interaction analysis in pancreatic neuroendocrine tumors.

ABSTRACT

OBJECTIVE: Pancreatic neuroendocrine tumors are relatively rare pancreatic neoplasms over the world. Investigations of the molecular biology of PNETs are insufficient for nowadays. We aimed to explore the expression of microRNA and messenger RNA and regulatory processes underlying pancreatic neuroendocrine tumors. MATERIALS AND METHODS: The messenger RNA and microRNA expression profile of GSE43796 were downloaded, including 6 samples with pancreatic neuroendocrine tumors and 5 healthy samples. First, the Limma package was utilized to distinguish the differentially expressed messenger RNA and microRNA separately. Then we used microRNA Walk databases to predict the target genes of the differentially expressed microRNAs (DE-microRNAs), and selected differentially expressed target genes whose expression was reversely correlated with microRNAs. Gene Ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to explore the functions and pathways of target genes. In addition, we constructed a regulatory miRNAs-target genes network and a protein-protein interaction network. RESULTS: There were 28 differentially expressed microRNAs and 859 differentially expressed messenger RNAs, including 253 potential target genes. These target genes mainly enriched in ABC transporters pathway. In this network, hsa-miR-7-2-3p demonstrated the highest connectivities whereas KLF12 was the mRNAs with the highest connectivities. CXCL12 was identified as the hub of the protein-protein interaction sub-network. CONCLUSIONS: The genes involved in ABC transporters and Type II diabetes mellitus pathway, KLF12 and CXCL12 may play an important role in the progression of pancreatic neuroendocrine tumors. However, more experimental studies are required.