Dysregulation of microRNA in cholangiocarcinoma identified through a meta-analysis of microRNA profiling.

BACKGROUND In the past decades, the potential of microRNA (miRNA) in cancer diagnostics and prognostics has gained a lot of interests. In this study, a meta-analysis was conducted upon the pooled miRNA microarray data of cholangiocarcinoma (CCA). AIM To identify differentially expressed (DE) miRNAs and perform functional analyses in order to gain insights to understanding miRNA-target interactions involved in tumorigenesis pathways of CCA. METHODS Raw data from 8 CCA miRNA microarray datasets, consisting of 443 samples in total, were integrated and statistically analyzed to identify DE miRNAsviacomparison of levels of miRNA expression between CCA and normal bile duct samples usingt-tests (P< 0.001). The 10-fold cross validation was performed in order to increase the robustness of thet-test results. RESULTS Our data showed 70 up-regulated and 48 down-regulated miRNAs in CCA. Gene Ontology and pathway enrichment analyses revealed that mRNA targets of DE miRNAs were significantly involved in several biological processes. The most prominent dysregulated pathways included phosphatidylinositol-3 kinases/Akt, mitogen-activated protein kinase and Ras signaling pathways. CONCLUSION DE miRNAs found in our meta-analysis revealed dysregulation in major cancer pathways involved in the development of CCA. These results indicated the necessity of understanding the miRNA-target interactions and the significance of dysregulated miRNAs in terms of diagnostics and prognostics of cancers.