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.

Inhibition of miR-155 reduces impaired autophagy and improves prognosis in an experimental pancreatitis mouse model

“…TAB2 is a target gene of miR-155 that is directly inhibited by this miRNA. Regarding pancreatitis, miR-155 expression levels were higher in patients with acute and chronic pancreatitis than in healthy controls, and thus, miR-155 levels should be associated with local and systemic inflammation 7,34 . Our study shows that AAV-9-mediated miR-155 delivery was efficient in the pancreas, and the expression of the target gene TAB2 was visibly regulated.…”

“…In particular, the dysregulation of miR-155 has been strongly implicated in Helicobacter pylori -related gastric disease, inflammatory bowel disease, and colorectal cancer through its involvement in molecular changes in important targets and signaling pathways 6 . A previous study showed that miR-155 was upregulated in pancreatitis samples compared with control samples by performing a comprehensive bioinformatics analysis 7 . In the course of AP, the upregulation of miR-155 may promote pancreatic inflammation through its target proteins.…”

Pilot study identifying circulating miRNA signature specific to alcoholic chronic pancreatitis and its implication on alcohol‐mediated pancreatic tissue injury

“…A list of miRNAs expressed in CP tissue was manually curated from previously published literature. [11][12][13][14][15] The list was expanded using miRNAs in pancreatic tissue identified from miRmine, 16 which is a database containing a collection of expression profiles from different publicly available miRNA-seq data sets.…”

Reciprocal Feedback Loop of the MALAT1-MicroRNA-194-YAP1 Pathway Regulates Progression of Acute Pancreatitis

“…miRNAs, 18 to 22 nucleotides in length, are noncoding RNAs that regulate post-transcriptional expression of target genes and participate in a variety biological processes [38, 39]. Increasing evidence suggests that multiple miRNAs are dysregulated in AP patients and are involved in the pathogenesis of pancreatitis [40]. To explore whether miRNAs also regulate the level of YAP1 expression in AP models, we used bioinformatics method to analyze the expression profile of miRNAs using the public microarray data of GSE24279.…”