Long non-coding RNA-ROR aggravates myocardial ischemia/reperfusion injury

Abstract

Long non-coding RNAs (lncRNAs) play an important role in the pathogenesis of cardiovascular diseases, especially in myocardial infarction and ischemia/reperfusion (I/R). However, the underlying molecular mechanism remains unclear. In this study, we determined the role and the possible underlying molecular mechanism of lncRNA-ROR in myocardial I/R injury. H9c2 cells and human cardiomyocytes (HCM) were subjected to either hypoxia/reoxygenation (H/R), I/R or normal conditions (normoxia). The expression levels of lncRNA-ROR were detected in serum of myocardial I/R injury patients, H9c2 cells, and HCM by qRT-PCR. Then, levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) were measured by kits. Cell viability, apoptosis, apoptosis-associated factors, and p38/MAPK pathway were examined by MTT, flow cytometry, and western blot assays. Furthermore, reactive oxygen species (ROS) production was determined by H2DCF-DA and MitoSOX Red probes with flow cytometry. NADPH oxidase activity and NOX2 protein levels were measured by lucigenin chemiluminescence and western blot. Results showed that lncRNA-ROR expression was increased in I/R patients and in H/R treatment of H9c2 cells and HCM. Moreover, lncRNA-ROR significantly promoted H/R-induced myocardial injury via stimulating release of LDH, MDA, SOD, and GSH-PX. Furthermore, lncRNA-ROR decreased cell viability, increased apoptosis, and regulated expression of apoptosis-associated factors. Additionally, lncRNA-ROR increased phosphorylation of p38 and ERK1/2 expression and inhibition of p38/MAPK, and rescued lncRNA-ROR-induced cell injury in H9c2 cells and HCM. ROS production, NADPH oxidase activity, and NOX2 protein levels were promoted by lncRNA-ROR. These data suggested that lncRNA-ROR acted as a therapeutic agent for the treatment of myocardial I/R injury.

Long non‑coding RNA GAS5 regulates myocardial ischemia‑reperfusion injury through the PI3K/AKT apoptosis pathway by sponging miR‑532‑5p

“…Subsequent to intervention, significant positive results were revealed in subsequent functional tests (33). In addition, the data revealed that the expression levels of lncRNA-regulator of reprogramming was significantly increased by nearly 2-fold compared with the control group in the ischemia-reperfusion injury group (34). Therefore, the upregulation of lncRNA is notable.…”

Retracted Article: Long noncoding RNA ANRIL protects cardiomyocytes against hypoxia/reoxygenation injury by sponging miR-195-5p and upregulating Bcl-2

“…2,20 In the present study, our data supported that H/R induced myocardial cell injury, as evidenced by the repression of cell proliferation and the promotion of cell apoptosis, in accordance with previous studies. 25,26 Subsequently, we further explored the effect and underlying mechanism of ANRIL on AMI by H/Rinduced myocardial cells. ANRIL is an attractive lncRNA encoded in the 9p21 locus, which plays an important role in disease-associated polymorphisms.…”

KCNQ1OT1, HIF1A‐AS2 and APOA1‐AS are promising novel biomarkers for diagnosis of coronary artery disease

“…LncRNAs have emerged as important regulators in various pathological processes that contribute to the development of several diseases . Some lncRNAs are also involved in the development of CVDs, including heart failure, cardiac hypertrophy, cardiometabolic diseases, and myocardial infarction . Various lncRNAs have been shown to control the functions of vascular smooth muscle cells, endothelial cells and macrophages .…”