Long non-coding RNA LUCAT1 inhibits myocardial oxidative stress and apoptosis after myocardial infarction via targeting microRNA-181a-5p

Abstract

This study hoped to explore the effects and mechanism of long non-coding RNA (lncRNA) LUCAT1 regulating microRNA-181a-5p (miR-181a-5p) on oxidative stress and apoptosis of cardiomyocytes induced by H 2 O 2 . Totally, 72 patients with acute myocardial infarction (AMI) were included. H9c2 cardiomyocytes were cultured in vitro, and the H 2 O 2 model of cardiomyocytes was established. The expression levels of LUCAT1 and miR-181a-5p were detected by qRT-PCR after H 2 O 2 induction. The contents of reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) in cells were detected. The survival rate of the cells was detected by the Cell Counting Kit-8 (CCK-8) method; the apoptosis was detected by flow cytometry. The luciferase reporter experiment and quantitative real-time PCR (qRT-PCR) were used to verify the targeted relationship between LUCAT1 and miR-181a-5p. LUCAT1 was lowly expressed in the AMI patients. After H 2 O 2 induction, the expression of LUCAT1 in H9c2 cells lessened significantly, while the expression of miR-181a-5p elevated significantly ( P < 0.001). Transfection of p-LUCAT1 significantly reversed the decreased SOD levels, the increased MDA and ROS content, and the elevated tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) in H 2 O 2 -stimulated cells ( P < 0.001). Upregulation of LUCAT1 contributed to the mitigation of H 2 O 2 injury by promoting viable cells and repressing apoptotic cells ( P < 0.01). LUCAT1 targeted miR-181a-5p and negatively regulated miR-181a-5p expression ( P < 0.001). Collectively, LUCAT1 played a protective role on oxidative stress injury, inflammation, viability, and apoptosis of cardiomyocytes induced by H 2 O 2 via regulating miR-181a-5p.

Inflammation and Oxidative Stress Role of S100A12 as a Potential Diagnostic and Therapeutic Biomarker in Acute Myocardial Infarction

“…Zhang et al demonstrated that the inhibition of death-associated protein kinase 1 (DAPK1) expression inhibited inflammation and oxidative stress and protected rats from myocardial injury caused by myocardial infarction [ 55 ]. In addition, a study by Xiao et al showed that the overexpression of lung cancer associated transcript 1 (LUCAT1) has a protective effect on AMI by inhibiting the effects of H 2 O 2 on oxidative stress, inflammation, viability, and apoptosis in H9c2 cells [ 56 ]. Therefore, we speculate that inhibiting the expression of S100A12 could inhibit oxidative stress and inflammation, thereby exerting a similar cardioprotective effect and reducing myocardial injury.…”

Oxycodone protects cardiac microvascular endothelial cells against ischemia/reperfusion injury by binding to Sigma-1 Receptor

“…Myocardial infarction is a common and serious clinical disease and a threat to public health worldwide in the future and tissue damage caused by myocardial ischemia is an important cause of fatal diseases [ 22 , 23 ]. In the present study, the protective effects of Oxycodone on myocardial I/R injury were investigated in vivo and in vitro.…”

The Role of ncRNAs in Cardiac Infarction and Regeneration

“…Several in vitro and in vivo studies have demonstrated that high levels of miR-181 lead to the inhibition of myocardial inflammation via the modulation of pro-inflammatory markers (such as tumor necrosis factor-α (TNF-α) and IL-1β) and oxidative stress; through the regulation of ROS components such as SOD1 (superoxide dismutase 1) and SOD2; and by targeting ATF2 (activating transcription factor 2) ( Figure 1 ) [ 38 , 39 ]. Moreover, LUCAT1 and MIAT lncRNAs are regulators of miR-181a-5p, thereby modulating inflammation (TNF-α, IL6, and IL1β), oxidative stress (SOD levels), apoptosis, and cell viability in vitro, which was demonstrated in an in vitro model of CM injury or ischemia–reperfusion, as well as in vivo by modulating the JAK/STAT signaling pathway ( Figure 1 ) [ 40 , 41 ].…”

“…In this context, several lncRNAs can modulate miRNAs and play essential roles in cardiac inflammation, such as KCNQ1OT1 lncRNA, which sponges miR-130 and thus modulates ZNF91 (zinc finger protein 91), and Lucat1 lncRNA, which sponges miR-181. However, the molecular mechanisms relating them to cardiac inflammation remain largely elusive [ 40 , 83 ]. Additionally, other lncRNAs modulating miRNAs have emerging roles in cardiac inflammation, such as HULC lncRNA, which modulates the expression of miR-29 and miR-377, leading to the regulation of the NLRP3/Caspase-1/IL-1β signaling pathway, while TTTY15 lncRNA modulates miR-98 and, thereafter, CRP expression [ 192 , 194 , 195 ].…”