Dauricine inhibits human pancreatic carcinoma cell proliferation through regulating miRNAs

Abstract

Pancreatic cancer is one of the most malignant digestive tract tumors with the worst prognosis. Dauricine (Dau) can inhibit the proliferation of the pancreatic cancer cell line, and has the potential to be used as an adjuvant drug against pancreatic cancer; however, the working mechanism of Dau has not been elucidated. To unravel the effects and mechanisms of Dau on proteins and metabolic pathways, we evaluated the mRNA and microRNA expression in BxPC3 cells treated with Dau. The differences in the gene expression were compared using principal component analysis using mRNA and miRNA data to detect and analyze the sample discrimination. 187 miRNA and 907 mRNA that were significantly differentially expressed were identified using Python programming. On comparing genes and miRNAs in the DISEASES database, 79 known miRNA and 47 mRNA were found to be affected by Dau. The up-regulated and down-regulated genes were annotated with GO biological processes to determine the functional effect. Interactions between mRNA and mRNA were analyzed using the STRING database and the miRBase database was queried to obtain experimentally verified interactions between miRNA and mRNA as edges of miRNA and mRNA in the network. Finally, 413 sites and 2125 sides of the network were obtained, including 1 up-regulated and 18 down-regulated miRNAs. The expression of 19 miRNAs was identified by qPCR. The analysis of the protein–protein interaction network, using the Molecular Complex Detection (MCODE) plug-in of cytoscape, helped in identifying 12 important sub-networks. Most subnets are indirectly or directly related to specific miRNAs. This study provides evidence for the anticancer effect of Dau as a potential anticancer compound.