Integrated analysis of ovarian cancer stem cells-associated lncRNA-miRNA-mRNA network via microarray and Gene Expression Omnibus database

Abstract: Background Competing endogenous RNAs (CeRNAs) play an important role in maintenance of ovarian cancer stem cells (OCSCs) characteristics. Objective To isolate a new OCSC line and construct a ceRNA network for maintenance of OCSCs characteristics by the cell line and GEO Database. Methods We isolated OCSCs from ovarian cancer cell line COC1 by chemotherapy drugs and growth factors. We identified the DEMs, DELs and DEGs between OCSCs and COC1 by microarray and combined them with representative microarray profiles in GEO Database. The ceRNA network was constructed by STRING and Cytoscape. QPCR and western blot were used to verify the expression of several genes that contained in the predicted network. Results According to the combination, 28 DEMs were identified at first, and 452 DEGs were obtained combining with the predicted targets of these miRNAs and our mRNA microarray results. Up-regulated DEGs of them were significantly enriched in ‘p53 signaling pathway’, ‘FoxO signaling pathway’, et al, whereas down-regulated DEGs were significantly enriched in ‘Adherens junction’ and ‘Hepatitis C’ pathway. Finally, we obtained OCSCs characteristics related ceRNA network with 10 DEMs, 21 DEGs, and 25 transcripts of 13 DELs. We verified that LINC00665-miR-146a-5p-NRP2 should be one of the pathways of the constructed ceRNA network. Conclusion The ceRNA network we constructed may be involved in the stem cell characteristics maintenance of OCSCs and provide directions for further OCSCs research in the future.