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

Abstract

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-1β, 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.

CircNFIC Balances Inflammation and Apoptosis by Sponging miR-30e-3p and Regulating DENND1B Expression

“…Furthermore, circFOXO3 can interact with ID-1, E2F1, FAK, and HIF1α and increase cellular senescence [58]. Compared to the description above, more circular RNAs were reported to function as a microRNA sponge [19,21,59]. To explore that mechanism, the RNA pull-down, dual-luciferase reporter assay, and the RNA FISH assay were carried out, and many qRT-PCRs were performed.…”

“…Due to its special ring structure, circRNA has strong resistance to RNase R digestion and inherit conservation [14,16,17], which can also be used as new biomarkers of some diseases. Since 2011, Salmena proposed the ceRNA hypothesis [18], where an increasing number of circRNAs have been found to act as sponges, playing a regulator role [19][20][21], which consist of one or multiple exons [22]. Some studies found that circRNAs played an important role in the polarization and apoptosis of macrophages [23,24] and regulated the inflammation response of macrophages exposed to lipopolysaccharide (LPS) [25,26].…”

A four-lncRNA risk signature for prognostic prediction of osteosarcoma

“…RNA extraction and qRT-PCR analysis were carried out as described in our previous study ( Zhang et al, 2021a ). Total RNA from cultured cells was extracted using SparkZol reagent (SparkJade, Shandong, China), and cDNA was synthesized with the Evo M-MLV RT Premix for qPCR (AG11706, Accurate Biotechnology, Hunan, China).…”

hsa_circ_0060975 is highly expressed and predicts a poor prognosis in gastric cancer

“…The inclusion criteria of healthy volunteers were as follows: i) No abnormality in all indices of physical examination; ii) the same physical examination time as that of an additional 126 patients with GC; and iii) blood samples could be obtained. Exclusion criteria of the healthy volunteers were as follows: i) No history of malignant tumor, chronic inflammation and mental illness; and ii) acute inflammation or recovery period, which may affect the expression of circRNAs ( 29 , 30 ). The blood samples were centrifuged at 1006.2 × g for 15 min at room temperature and then 4 ml of plasma samples were collected.…”