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Published on: May 21, 2019
Identfication of key miRNAs in pancreatitis using bioinformatics analysis of microarray data
Dadong Wang1, Zi-Man Zhu1, Yu-Liang Tu1
1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, P.R. China.
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.
Insights
This study identified specific microRNAs (miRNAs) linked to pancreatitis by analyzing gene expression data. These pancreatitis-associated miRNAs and their target genes offer potential new therapeutic targets for managing pancreatic inflammation.
Area of Science:
- Molecular Biology
- Genomics
- Biochemistry
Background:
- Pancreatitis is a significant pancreatic inflammation, often caused by alcohol and gallstones.
- MicroRNAs (miRNAs) play crucial roles in regulating gene expression and are implicated in various diseases.
- Identifying specific miRNAs involved in pancreatitis pathogenesis is essential for developing targeted therapies.
Purpose of the Study:
- To identify differentially expressed microRNAs (DE-miRNAs) associated with pancreatitis.
- To predict target genes of these DE-miRNAs and analyze their functions.
- To construct a regulatory network of pancreatitis-associated genes and miRNAs for potential therapeutic insights.
Main Methods:
- Analysis of the GSE24279 microarray dataset containing pancreatitis and normal control samples.
- Screening for DE-miRNAs using the Limma package.
- Target gene prediction using miRecords and miRWalk databases.
- Functional and pathway enrichment analysis using DAVID.
- Identification of pancreatitis-associated genes using the Comparative Toxicogenomics Database.
- Construction of a miRNA-gene regulatory network using Cytoscape.
Main Results:
- 14 upregulated and 39 downregulated miRNAs were identified in pancreatitis samples.
- 290 target genes of DE-miRNAs were determined, with 279 identified as pancreatitis-associated.
- Key genes like CCND1, AKT2, CDK6, and SMAD2 were linked to pancreatic cancer pathways.
- A regulatory network revealed 37 miRNAs targeting pancreatitis-associated genes.
- Specific miRNAs (hsa-miR-15a, hsa-miR-16, hsa-miR-155, hsa-miR-375, hsa-miR-429) showed potential roles in pancreatitis pathogenesis.
Conclusions:
- Several miRNAs and their target genes are significantly associated with pancreatitis.
- These identified miRNAs and their targets represent potential biomarkers and therapeutic targets for pancreatitis.
- The study provides a foundation for further research into miRNA-based interventions for pancreatitis.

