Molecular Mechanism Exploration of Pancreatitis Based on miRNA Expression Profile

Pancreatitis is a popular disease around the world, and can also lead to pancreatic cancer. Pancreatitis can be distinguished into two types, acute pancreatitis (AP) and chronic pancreatitis (CP). Every year, AP leads to approximately 275,000 new cases and is the most frequent gastrointestinal disease in American.

The miRNA expression profile of pancreatic cancer and pancreatitis was downloaded from GEO with accession id GSE24279. First, the differentially expressed miRNAs with |fold change| ≥ 2 and p-value ≤ 0.05 and then the target genes of significantly differentially expressed miRNAs in pancreatitis were identified and the interaction network was constructed. Also the biological functions of the target genes were explored based on GO and KEGG enrichment. Finally, the expression values of hsa-miR-373-5p and hsa-miR-374a-5p were validated using RT-PCR.

A total of 40 and 13 differentially expressed miRNAs were screened out for pancreatic and pancreatitis, respectively. Two miRNAs, hsa-miR-373-5p and hsa-miR-374a-5p, had significantly down-regulated expression in pancreatitis. Target gene analysis showed that hsa-miR-373-5p probably participates in the development of pancreatitis by regulating MBL2, MAT2B, and BCL10. In addition, has-miR-374a-5p can regulate the expression of NCK1, MMP14. Those genes are involved in nuclear factor kappa B and p38 signaling in the early stage of pancreatitis. Also, NCK1 can regulate pancreatic β-cell proinsulin content and participate in the progression of pancreatic cancer development.

In summary, the findings in this study deciphered the potential miRNA regulation mechanism in pancreatitis, and identified valuable biomarkers for the diagnosis of pancreatitis.