Circular RNA circACSL1 aggravated myocardial inflammation and myocardial injury by sponging miR-8055 and regulating MAPK14 expression.

Myocarditis (MC) is a common, potentially life-threatening inflammatory disease of the myocardium. A growing body of evidence has shown that mitogen-activated protein kinase 14 (MAPK14) participates in the pathogenesis of MC. However, the upstream regulators of MAPK14 remain enigmatic. Circular RNAs (circRNAs) have been identified to play vital roles in the pathophysiology of cardiovascular diseases. Nevertheless, the clinical significance, biological function, and regulatory mechanisms of circRNAs in MC remain poorly understood. In this study, we determined a novel circRNA, circACSL1 (ID: hsa_circ_0071542), which was significantly upregulated in the acute phase of MC, and its dynamic change in expression was related to the progression of MC. We used lipopolysaccharide (LPS) to induce the inflammatory responses in the human cardiomyocytes (HCM) line for in vitro and in cellulo experiments. The pro-inflammatory factors (IL-1ß, IL-6, and TNF-α), myocardial injury markers (cTnT, CKMB, and BNP), cell viability, and cell apoptosis were measured to evaluate the extent of myocardial inflammation and myocardial injury level. Functional experiments, including gain-of-function and loss-of-function, were then performed to investigate the pro-inflammatory roles of circACSL1. The results revealed that circACSL1 could aggravate inflammation, myocardial injury, and apoptosis in HCM. Mechanistically, circACSL1 acted as a sponge for miR-8055-binding sites to regulate the downstream target MAPK14 expression. Furthermore, overexpression of miR-8055 rescued the pro-inflammatory effects of circACSL1 on HCM, and the upregulation of MAPK14 induced by circACSL1 was attenuated by miR-8055 overexpression. Knockdown of circACSL1 or overexpression of miR-8055 reduced myocardial inflammation and myocardial injury level and these effects were rescued by overexpression of MAPK14. In summary, our study demonstrated that circACSL1 could aggravate myocardial inflammation and myocardial injury through competitive absorption of miR-8055, thereby upregulating MAPK14 expression. Moreover, circACSL1 may represent a potential novel biomarker for the precise diagnosis of MC and offer a promising therapeutic target for MC treatment.

Differential Expression Profiles and Functional Analysis of Long Non-coding RNAs in Children With Dilated Cardiomyopathy.

Aim: To evaluate the expression profile of long non-coding RNAs (lncRNAs) in different left ventricular function of dilated cardiomyopathy (DCM) in children and explore their possible functions. Methods: The lncRNA microarray experiment was used to determine the differential expression profile of lncRNA in three children with DCM and three healthy volunteers. The functional analysis and the construction of the lncRNA-mRNA interaction network were carried out to study the biological functions. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to verify the microarray data. Results: There were 369 up-regulated lncRNAs identified in the DCM patients (fold change >2, P < 0.05), and 505 down-regulated lncRNAs. Based on target gene prediction and co-expression network construction, 9 differentially expressed lncRNAs were selected for the PCR to verify the accuracy of the microarray data, of which 5 were up-regulated and 4 were down-regulated, and finally proved that 7 of them were consistent with the trend of microarray data results. Four of these lncRNAs had significant differences between the patients with poor cardiac function and patients with improved left ventricle function. Conclusion: LncRNAs may play an important role in pediatric DCM and may provide a new perspective for the pathogenesis, diagnosis, and treatment of this disease.

Differential Expression Profiles and Functional Prediction of Circular RNAs in Pediatric Dilated Cardiomyopathy.

Circular RNAs (circRNAs) have emerged as essential regulators and biomarkers in various diseases. To assess the different expression levels of circRNAs in pediatric dilated cardiomyopathy (PDCM) and explore their biological and mechanistic significance, we used RNA microarrays to identify differentially expressed circRNAs between three children diagnosed with PDCM and three healthy age-matched volunteers. The biological function of circRNAs was assessed with a circRNA-microRNA (miRNA)-mRNA interaction network constructed from Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Differentially expressed circRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in 25 children with PDCM and 25 healthy volunteers. We identified 257 up-regulated (fold change ≤ 0.5, P < 0.05) and 899 down-regulated (fold change ≥2, P < 0.05) circRNAs in PDCM patients when compared to healthy volunteers. The qRT-PCR experiments confirmed has_circ_0067735 down-regulation (0.45-fold, P < 0.001), has_circ_0070186 up-regulation (2.82-fold, P < 0.001), and has_circ_0069972 down-regulation (0.50-fold, P < 0.05). A functional analysis of these differentially expressed circRNAs suggests that they are associated with hypertrophy, remodeling, fibrosis, and autoimmunity. CircRNAs have been implicated in PDCM through largely unknown mechanisms. Here we report differentially expressed circRNAs in PDCM patients that may illuminate the mechanistic roles in the etiology of PDCM that could serve as non-invasive diagnostic biomarkers.