MicroRNA-224 is downregulated in mucinous cystic neoplasms of the pancreas and may regulate tumorigenesis by targeting Jagged1.

The underlying malignancy of mucinous cystic neoplasms (MCNs) of the pancreas most commonly results in patients undergoing surgery. The tumorigenesis of MCNs remains elusive and few studies have investigated the role of specific micro (mi)RNAs in MCNs. The present study focused on the expression of miRNA-224 and its putative target gene Jagged1 (Jag1) to examine its role in tumorigenesis and its suitability as a biomarker for MCNs. Paired tissue samples confirmed by surgical pathology were used to screen the miRNAs involved in MCNs with miRNA microarrays (n=3), and to verify the differentially expressed miRNAs (n=3) and mRNAs of candidate target genes of miRNAs by quantitative polymerase chain reaction (qPCR; n=8). Immunohistochemistry was conducted to confirm the expression and location of Jag1 in the neoplastic epithelial cells. Luciferase assays were performed to confirm the direct target gene of miRNA-224. miRNA microarray analysis revealed that two differentially expressed miRNAs were closely associated with tumorigenesis and pancreatic diseases. The qPCR results revealed that miRNA-224 was more significantly aberrantly expressed and the mRNA expression levels of its putative target gene, Jag1, were upregulated. Strong, diffuse cytoplasmic immunohistochemical labeling of Jag1 with occasional nuclear labeling was detected in the mucinous epithelium. Luciferase reporter activity was significantly reduced by co-transfected miRNA-224 mimics and pMIR-Jag1-wild-type, which suggested that miRNA-224 bound to recognition sites in the 3' untranslated region of its target mRNA, Jag1. In conclusion, miRNA-224 was downregulated in MCNs and may regulate tumorigenesis by targeting Jag1. Further studies investigating the role of miRNAs and functional analysis of epigenetic alterations are required to examine the diagnostic and therapeutic potential of miRNAs in MCNs. [ABSTRACT FROM AUTHOR]