ObjectiveThe diagnostic value of circulating circular RNAs (circRNAs) has received more and more attention. However, little has been reported about their potential in the diagnosis of congenital heart diseases (CHD). In this study, we explored differential expression of circRNAs from children with CHD to evaluate their potential as clinical biomarkers.MethodsWe established a discovery cohort (four CHD cases; four matched healthy controls) and a validation cohort (40 CHD cases; 40 matched healthy controls). Microarray expression analysis was performed on the discovery set to identify candidate circRNAs. Candidates were further validated in the validation set. The diagnostic accuracy of circRNAs was determined by receiver operating characteristic (ROC) analysis. Gene ontology (GO), pathway, and network analysis were performed to predict a network of circRNA/miRNA and target mRNAs related to CHD.ResultsThe top seven significantly differentially expressed CHD‐associated circRNAs were validated by RT‐PCR as follows: hsa_circRNA_004183, hsa_circRNA_079265, hsa_circRNA_105039, hsa_circRNA_404686, hsa_circRNA_101050, hsa_circRNA_100787, and hsa_circRNA_101328. Three significantly down‐regulated circRNAs (hsa_circRNA_004183, hsa_circRNA_079265, and hsa_circRNA_105039) were identified with area under curve (AUC) values of 0.758, 0.809, and 0.907, respectively; the combination had an AUC of 0.965. An interaction network was constructed by 43 circRNAs, 9 miRNAs, and 29 mRNAs, which involved in heart development.ConclusionsWe identified three circRNAs under‐expressed in plasma from children with CHD. These circRNAs may be crucial in the development of CHD and may serve as novel non‐invasive biomarkers for the diagnosis of CHD in children.
Background ACE2 plays a particular role in the changes in multiple organ functions. However, whether ACE2 expression differs at different ages and whether it plays a role in infection-related organ dysfunction remains unclear. Methods Female and male C57BL/6 mice in four different age groups were included in this study. Immunohistochemical and Western blot analyses were performed to evaluate ACE2 expression characteristics in lung tissues. At the same time, we detected the changes of ACE2 in human blood of different ages and evaluated its clinical significance in sepsis-associated organ dysfunction (SAOD). Results This study indicated that ACE2 is expressed differently in mouse lung tissues at four different ages (P < 0.05). The peak expression distribution of ACE2 in lung tissues was in the newborn and middle-aged cohorts (P < 0.05). Infants younger than one year had a significantly higher concentration of ACE2 in serum and enhanced susceptibility compared with other ages (P < 0.05). Serum APTT, D-dimer, LDH, and PCT, as well as ACE2 in sepsis and SAOD groups, were statistically significant (P < 0.05) and were related to an increased risk of SAOD. There was a positive correlation between ACE2 and D-dimer (P < 0.05). Conclusion The levels of ACE2 expression varied in different age groups. It tends to be higher in infants and young children. This result suggests that young children are more susceptible to infection. Moreover, a cutoff value for the ACE2 level >1551.15 pg/mL and D-dimer >984.5 U/L should be considered a warning sign of infection-associated organ dysfunction and guide the clinician in evaluating the patient’s multiple organ function.
Circular RNAs (circRNAs) are novel endogenous RNAs with vital roles in the pathology of various diseases. However, their role in sepsis-induced lung injury is unknown. In this study, high-throughput gene sequencing was used to analyze the expression profiles of circRNAs in lung specimens of mice grouped by acute lung injury induced by cecal ligation and puncture (CLP) and sham. To identify differentially expressed circRNAs, the left lungs of sham ( n = 3) and CLP ( n = 3) mice were used for high-throughput sequencing. A total of 919 circRNAs were identified. Of these, 38 circRNAs showed significantly different expression levels between the groups ( P < 0.05, fold change ≥2). The levels of 20 circRNAs were up-regulated and those of 18 others were down-regulated. In bioinformatics analysis of the source genes of these circRNAs, the genes were closely associated with the inflammatory response (e.g., the TGF-β, MAPK, Fc gamma R-mediated phagocytic, and VEGF pathways). Eight circRNAs with large intergroup differences, small intragroup differences, and high expression were selected for further validation by qRT-PCR. Two of the eight were significantly different. These two circRNAs were annotated with circRNA/miRNA interaction information downloaded from the TargetScan and miRanda databases and visualized. Our results provide novel insights into the roles of circRNAs in sepsis-induced acute lung injury.
Circular RNAs (circRNAs), a novel type of endogenous RNAs, can function as microRNA (miRNA) sponges capable of regulating gene transcription, binding to RNA-associated proteins, and even encoding proteins. CircRNAs are involved in various cell behaviors, such as proliferation and apoptosis. The mouse model has also been demonstrated to be similar to that of humans in many studies. To explore the profile of circRNAs during embryonic lung development and their potential functions in lung development-related diseases, mouse embryos at the pseudoglandular phase, canalicular phase, saccular phase, and alveolar phase were collected. High-throughput sequencing was then used to identify a total of 1,735 circRNAs (junction reads !5 and p < 0.05). It is well known that the functions of circRNAs are related to host genes. In our study, bioinformatics analysis indicated that the screened host genes were closely associated with lung development and included the Hippo signaling pathway, PI3K-Akt signaling pathways, and TGF-β signaling pathways. Moreover, miRNA sponges are another mechanism involved in lung development. Therefore, we predicted many miRNAs binding to circRNAs, such as miR-17 and miR-20, using the TargetScan and miRanda databases. Previously, miRNAs were proven to be necessary for lung development. The peak expression of circRNAs is distributed at different time points, suggesting their involvement in different stages of embryonic mouse lung development.
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