Conclusion
The study revealed a regulatory network of UCA1-miR-107-ITGA2 and validated UCA1 and ITGA2 as potential prognostic factors for PaC.
Methods
LncRNA and mRNA microarrays were used to determine the expression profiles in PaC cells. Analysis of Kyoto Encyclopedia of Genes and Genomes pathway was performed to identify pathways associated with differentially expressed mRNAs. Coexpression profiles were identified by constructing differentially expressed lncRNA-mRNA regulatory network and further validated by quantitative real-time polymerase chain reaction assay and western blot assay. The bioinformatics computational method was applied to predict the biological target of lncRNA and mRNA, which was identified by luciferase reporter assay. Migration/invasion ability and apoptosis rate of cells were assessed by transwell assay and flow cytometry assay.
Results
It was identified that the level of urothelial cancer associated 1 (UCA1) was increased in PaC cells, and the inhibition of UCA1 suppressed migration and invasion ability of the cancer cells. The luciferase reporter assay recognized that miR-107 was targeted by UCA1, and integrin subunit α 2 (ITGA2) was further targeted by miR-107. This confirmed the prediction of lncRNA-miRNA-mRNA regulation mechanism. In the regulatory pathways, UCA1 and ITGA2 promoted PaC progression via focal adhesion pathway related proteins such as ITGA3, SRC protooncogene/nonreceptor tyrosine kinase, protein tyrosine kinase 2, and AKT serine/threonine kinase 1.