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CircRNAs are involved in a variety of human diseases, however, the expression profiles and the potential diagnostic value of circRNAs in human acute Stanford type A aortic dissection (AAAD) remains largely unknown. In this study, high-throughput RNA sequencing (RNA-Seq) was used to investigate the differentially expressed circRNAs, microRNAs (miRs) and mRNAs in human AAAD tissues (n = 10) compared with normal aortic tissues (n = 10). The results of RNA-Seq revealed that 506 circRNAs were significantly dysregulated (P<0.05, false discovery rate, FDR<0.05, fold change>2). The subsequent weighted gene correlation network analysis and the following co-expression network analysis revealed that tyrosine-protein kinase Fgr might play important roles in the occurrence and development of AAAD. According to the circRNA-miRNA-mRNA network, we found that the upstream regulatory molecule of Fgr is circMARK3. Finally, a receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of the serum circMARK3 as biomarkers for AAAD (cutoff value = 1.497, area under the curve = 0.9344, P < 0.0001, sensitivity = 90.0%, specificity = 86.7%). These results provided a preliminary landscape of circRNAs expression profiles and indicated that circMARK3 was a potential biomarker for AAAD diagnosis. [ABSTRACT FROM AUTHOR]

It has become increasingly clear that proper cellular control of pluripotency and differentiation is related to the regulation of rRNA synthesis. To further our understanding of the role that the regulation of rRNA synthesis has in pluripotency we monitored rRNA synthesis during the directed differentiation of human embryonic stem cells (hESCs). We discovered that the rRNA synthesis rate is reduced ~50% within 6 hours of ACTIVIN A treatment. This precedes reductions in expression of specific stem cell markers and increases in expression of specific germ layer markers. The reduction in rRNA synthesis is concomitant with dissociation of the Pol I transcription factor, UBTF, from the rRNA gene promoter and precedes any increase to heterochromatin throughout the rRNA gene. To directly investigate the role of rRNA synthesis in pluripotency, hESCs were treated with the Pol I inhibitor, CX-5461. The direct reduction of rRNA synthesis by CX-5461 induces the expression of markers for all three germ layers, reduces the expression of pluripotency markers, and is overall similar to the ACTIVIN A induced changes. This work indicates that the dissociation of UBTF from the rRNA gene, and corresponding reduction in transcription, represent early regulatory events during the directed differentiation of pluripotent stem cells. [ABSTRACT FROM AUTHOR]