The Emerging Roles Of Microvesicles MicroRNAs In Diagnosis And Pathogenesis Of Hepatocellular Carcinoma

PART â…  Comparison and bioinformatics analysis of microRNA profile in SMMC-7721cells and the corresponding microvesiclesObjective To define whether the microRNAs (miRNAs) in microvesicles (MVs) derived from tumor cells could mirror that of cells and analyze the potential roles of MVs in tumor microenvironment.Methods The presence and levels of888miRNAs from SMMC-7721cells and MVs were performed by Agilent miRNA microarray analysis. Bioinformatics tools were used to analyze functions of the identified miRNAs, including target genes prediction, gene ontology (GO) and pathway annotation.Results Of all the tested miRNAs,148miRNAs were co-expressed in MVs and SMMC-7721cells,121and15miRNAs were only detected in MVs and SMMC-7721cells, respectively. Bioinformatics analysis of the48common miRNAs with the similar expression level showed that among the3831target genes,78genes were known tumor genes. High enrichment GO terms were cell death and adhesion. Targets mainly involved in pathways of tumors, cell cycle and apoptosis, immune response, cell adhesion and metabolism.Conclusion MiRNAs in MVs could reflect the molecular signature of parent cells. MVs derived from SMMC-7721cells were potentially involved in carcinogenesis. PART â…¡ Comparison and bioinformatics analysis of microRNA profile in microvesicles derived from peripheral blood of hepatocellular carcinoma patients and normal controlsObjective To explore novel biomarkers for non-invasive diagnosis of hepatocellular carcinoma (HCC) and the potential roles of microRNAs (miRNAs) from circulating microvesicles (MVs) in HCC pathogensis.Methods The presence and levels of888miRNAs in MVs derived from the peripheral blood of HCC patients and normal controls were performed by Agilent miRNA microarray analysis. Bioinformatics tools were used to analyze functions of the altered miRNAs, including target genes prediction, protein interactions analysis, gene ontology (GO) and pathway annotation.Results Of all the tested miRNAs,381miRNAs were common in HCC and control group,4and75miRNAs were only detected in HCC and control, respectively. Compared with control group,115miRNAs were overexpressed with up to31fold changes (hsa-miR-671-5p) and127were underexpressed with up to0.041fold changes (hsa-miR-432) in HCC group. Bioinformatics analysis were applied to the top ten dysregulated miRNAs. By software STRING8, NOL3was found to be the core player among the300target genes of top ten up-regulated miRNAs and SRRM1was central among the219targets of the top down-regulated miRNAs.The underexpressed miRNAs were closely involved in the pathways of tumor, cell adhesion and immune response, such as MAPK signaling pathway, Wnt signaling pathway, chronic myeloid leukemia, cell adhesion molecules, antigen processing and presentation.Conclusion MiRNAs expression in MVs derived from peripheral blood of HCC patients changed aberrantly. The altered miRNAs may play roles in HCC pathogenesis according to the information exchanged mediated by MVs. PART â…¢ Comparison and analysis of microRNA profile in microvesicles derived from peripheral blood of liver disease patients and normal controlsObjective To explore the potential roles of microRNAs (miRNAs) from circulating microvesicles (MVs) in the process of chronic hepatitis B (CHB), hepatic cirrhosis (HC) and hepatocellular carcinoma (HCC).Methods The presence and levels of888miRNAs in MVs derived from the peripheral blood of liver disease patients and normal controls were performed by Agilent miRNA microarray analysis.Results Compared with control group,156miRNAs were overexpressed and222miRNAs were underexpressed in CHB group;64miRNAs were up-regulated and57miRNAs were down-regulated in HC group;115miRNAs increased and127miRNAs decreased in HCC group. After cross searching, we found that98dysregulated miRNAs were shared by CHB, HC and HCC group,46up-regulated miRNAs with the total fold change (FC) value up to199(hsa-miR-150*) and52decreased miRNAs in all the three groups with the total FC value up to0.249(hsa-miR-432).Conclusion The consistently and aberrantly expressed miRNAs in the MVs derived form peripheral blood of CHB, HC and HCC patients could predict the prognosis of CHB or HC patients and serve as surveillance markers, also may involve the initial carcinogensis of HCC.