Construction of an LncRNA-miRNA-mRNA network reveals functional Circulating miRNAs in pancreatic cancer

Backgrounds: Pancreatic ductal adenocarcinoma (PDAC) is the ۷th cause of cancer mortality.Uncovering possible plasma biomarkers are necessary to set effective therapeutic strategies at theearly stages of PDAC. MicroRNAs (miRNAs) are easily detectable biomarkers with delicatesensitivity and specificity in various cancers. This study introduces serum miRNAs expressionprofiles to find the most significant miRNAs in PDAC diagnosis.Materials and Methods: The plasma miRNA expression profile of fifteen cases was obtainedfrom the GEO (GSE۱۱۴۷۷۸). Differentially expressed miRNAs (DEMs) extraction wasaccomplished between healthy, pancreatitis, and PDAC samples using the limma package in R.|log۲FC| ≥۰.۵۸, and p-value< ۰.۰۵ cutoff were set to identify the significant DEMs. MiRNet toolwas used for target genes prediction of DEMs, including miRNAs and xeno-miRNAs. GeneOntology and pathway enrichment analyses were performed using the Pathview and ClueGO.Survival analysis by the Kaplan-Meier plot was also conducted to validate critical miRNAs andtarget genes.Results: A total of ۱۳۲ miRNAs showed significant up/down-regulation in PDAC samplescompared to healthy and pancreatitis samples. Our analyses introduced four novel key miRNAswith high node degrees in the network (miR-۳۷۸c, miR-۵۰۰a-۳p, miR-۱۲۷۰, and miR-۳۶۰۵-۵p).The NEAT۱ and KCNQ۱OT۱ were identified as important shared lncRNAs for the regulation ofthese potential diagnostic miRNAs. These potential markers of PDAC were classified asmiRNAs in cancer, PI۳K-Akt pathway, Hippo pathway, focal adhesion, regulation of cell cycle,and apoptotic pathway. The candidate miRNAs are also important in regulating critical genes,including bcl۲, klhl۱۵, gls, akt۱, and fyn which are downregulated in PDAC.Conclusion: In conclusion, our study demonstrates new insights into the significant miRNAsignatures of the PDAC prognosis and diagnosis. Identifying key miRNAs as candidate playersin PDAC may be reflected as potential new targets to improve treatment strategies in PDAC.

کلیدواژه ها:

Pancreatic ductal adenocarcinoma ، miRNA ، Serum biomarkers ، Bioinformatics ، Survival rate