Identfication of key miRNAs in pancreatitis using bioinformatics analysis of microarray data.

Abstract

Pancreatitis is a type of inflammation in the pancreas, which frequently occurs due to alcohol and gallstones. The present study aimed to identify pancreatitis-associated microRNAs (miRNAs) by analyzing the microarray of GSE24279. GSE24279 was downloaded from the Gene Expression Omnibus, composed of a collective of 27 pancreatitis and 22 normal control samples. The differentially expressed miRNAs (DE-miRNAs) in pancreatitis samples were screened using the Limma package in Bioconductor. Subsequently, target genes of the DE-miRNAs were predicted using the miRecords and miRWalk databases. Their potential functions were analyzed by functional and pathway enrichment analysis using the Database for Annotation, Visualization and Integrated Discovery online tool. Finally, pancreatitis-associated genes among the target genes identified were searched using the Comparative Toxicogenomics Database, and a regulatory network of pancreatitis-associated genes and their target miRNAs were constructed using Cytoscape software. A total 14 upregulated and 39 downregulated miRNAs were identified in pancreatitis samples compared with control samples and 290 target genes of DE-miRNAs were determined. Cyclin D1 (CCND1), v-akt murine thymoma viral oncogene homolog 2 (AKT2), cyclin-dependent kinase 6 (CDK6) and SMAD family member 2 (SMAD2) were involved in the pathway of pancreatic cancer. Among the target genes, 279 genes were pancreatitis-associated genes, which in turn were targeted by 37 miRNAs in the regulatory network. Hsa-miR-15a, hsa-miR-16, hsa-miR-155, hsa-miR-375 and hsa-miR-429 in particular may be involved in pancreatitis by targeting genes in the regulatory network, including hsa-miR-15a→CCND1, hsa-miR-16→CCND1, hsa-miR-155→CCND1/SMAD2, hsa-miR-375→AKT2/CDK6 and hsa-miR-429→CCND1. The above miRNAs and their targets may contribute to the pathogenesis of pancreatitis; therefore, they may be potential therapeutic targets.