NEAT1 promotes myocardial ischemia‐reperfusion injury via activating the MAPK signaling pathway

Abstract

Myocardial ischemia‐reperfusion (IR) injury is a common cardiovascular problem, which remains a major cause of death in the world. Emerging evidence has suggested that long noncoding RNAs are crucial players in myocardial injury. However, the functional involvement of nuclear enriched abundant transcript 1 (NEAT1) in myocardial IR injury remains poorly investigated. Our study focused on the mechanism of NEAT1 in myocardial IR injury. Here, we reported a crucial role for NEAT1 in exacerbating cardiac IR injury. NEAT1 was greatly increased in myocardial IR injury mice models. As exhibited knockdown of NEAT1 resulted in attenuated myocardial IR injury in vivo. In addition, we found that NEAT1 was dramatically induced by hypoxia/reoxygenation in H9c2 cells. Lactate dehydrogenase (LDH), malondialdehyde, reactive oxygen species levels, and endoplasmic reticulum stress‐regulated cardiomyocyte apoptosis were inhibited by the downregulation of NEAT1. Here, it was shown that knockdown of NEAT1 was able to repress tumor necrosis factor‐α, interleukin‐1β, and IL‐6 expression. The silence of NEAT1 protected against IR injury via decreasing troponin levels, cardiocytes apoptosis, creatine kinase, and lactate LDH release in vivo. Meanwhile, the mitogen‐activated protein kinase (MAPK) signaling was involved in NEAT1‐mediated myocardial IR injury. In summary, our data indicated that NEAT1 contributed to myocardial IR injury via activating the MAPK pathway.

Longnon‐coding RNA NEAT1 overexpression associates with increased exacerbation risk, severity, and inflammation, as well as decreased lung function through the interaction with microRNA‐124 in asthma

“…In addition, upregulation of lncRNA NEAT1 promotes ROS production and endoplasmic reticulum (ER) stress‐regulated cardiomyocyte apoptosis, aggravating the severity of ischemia‐reperfusion injury . Mechanically, increased serum level of ROS is a risk factor for high degree of airway obstruction, worse immune response, and asthma exacerbation, and ER stress induces the abnormal apoptosis as well as dysfunction of airway epithelial, which suggests the promoting role of lncRNA NEAT1 for the higher risk of exacerbation in asthma . Therefore, we deduced that lncRNA NEAT1 might be involved in the asthma exacerbation.…”

“…For example, lncRNA NEAT1 expression in peripheral blood mononuclear cells is remarkably increased in sepsis patients than that in HCs, and ROC curve illustrates that lncRNA NEAT1 is of good value in predicting sepsis risk with AUC 0.851 (0.812‐0.935) . In addition, upregulation of lncRNA NEAT1 promotes ROS production and endoplasmic reticulum (ER) stress‐regulated cardiomyocyte apoptosis, aggravating the severity of ischemia‐reperfusion injury . Mechanically, increased serum level of ROS is a risk factor for high degree of airway obstruction, worse immune response, and asthma exacerbation, and ER stress induces the abnormal apoptosis as well as dysfunction of airway epithelial, which suggests the promoting role of lncRNA NEAT1 for the higher risk of exacerbation in asthma .…”

Long noncoding RNA NEAT1 correlates with higher disease risk, worse disease condition, decreased miR‐124 and miR‐125a and predicts poor recurrence‐free survival of acute ischemic stroke

“…LncRNA NEAT1, as an abundant and ubiquitously expressed lncRNA, has been reported to be a pivotal factor in the pathology of various diseases, including cardiovascular and cerebrovascular diseases. [14][15][16] For example, a study shows that lncRNA NEAT1 is overexpressed in myocardial IR injury mice models and lncRNA NEAT1 knockdown represses levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), decreases troponin level, reduces cardiocytes apoptosis, and inhibits release of lactate LDH in vitro. 14 Besides, a study displays that lncRNA NEAT1 knockdown inhibits levels of IL-6, IL-1β, cyclooxygenase-2 (COX-2), and TNF-α via regulating miR-342-3p in human macrophages THP-1 cells.…”

“…[14][15][16] For example, a study shows that lncRNA NEAT1 is overexpressed in myocardial IR injury mice models and lncRNA NEAT1 knockdown represses levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), decreases troponin level, reduces cardiocytes apoptosis, and inhibits release of lactate LDH in vitro. 14 Besides, a study displays that lncRNA NEAT1 knockdown inhibits levels of IL-6, IL-1β, cyclooxygenase-2 (COX-2), and TNF-α via regulating miR-342-3p in human macrophages THP-1 cells. 15 For stroke, a study discloses that lncRNA NEAT1 upregulation enhances OGD/R injury-induced inflammatory response in cerebral microglial cells through Wnt/β-catenin signaling pathway.…”

“…12,13 Furthermore, the biological roles of lncRNA NEAT1 in cardiovascular and cerebrovascular diseases have been disclosed in some experiments, such as the promotion of lncRNA NEAT1 on inflammatory response in myocardial ischemia-reperfusion injury mice models and the inhibition of lncRNA NEAT1 knockdown on atherosclerosis-correlated events in vitro. 14,15 For stroke, previous study displays that lncRNA NEAT1 facilitates oxygen-glucose deprivation/reoxygenation (OGD/R) injury and neuroinflammation damage of microglial cells, meanwhile, lncRNA NEAT1 enhances intima thickening or vascular occlusion through modulating the phenotype conversion of vascular smooth muscle cells, together with excessive apoptosis of epithelial cells, indicating that lncRNA NEAT1 is a therapeutic target for ischemic stroke. 16,17 Based on these indications, we hypothesized that ln-cRNA NEAT1 might play a critical role in AIS development, progression, and prognosis, however, the related evidence was limited.…”