Abstract
BackgroundMyocardial reperfusion is an effective therapy for acute myocardial infarction (AMI). However, ischemia/reperfusion (I/R) injury following myocardial reperfusion is a significant limitation for AMI treatment. Five prime to Xist (FTX) was recognized as a biomarker of multiple diseases, including heart disease. However, the molecular mechanism of FTX in I/R injury is unclear.MethodsCell viability was evaluated by using cell counting kit-8 (CCK-8) assay. Apoptosis was analyzed by using a caspase-3 activity detection kit and flow cytometry. The expression of FTX, microRNA (miR)-150, and Kruppel-like factor 13 (KLF13) was measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The interaction of miR-150 and FTX or KLF13 was confirmed by a dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Protein expression of KLF13 was examined by Western blot. The role of FTX was detected in I/R-injured heart tissues in vivo.ResultsHydrogen peroxide (H2O2) induced cardiomyocyte injury by decreasing cell viability and expediting cell apoptosis. However, FTX alleviated cardiomyocyte injury by promoting cell proliferation and restricting cell apoptosis of H9C2 cells that were treated with H2O2. In addition, we discovered that FTX directly interacted with miR-150, while KLF13 was a target of miR-150. Rescue experiments showed that miR-150 neutralized the FTX-mediated promotion of cell progression and restriction of cell apoptosis in H9C2 cells treated with H2O2. KLF13 knockdown restored the effect of miR-150 on increased proliferation and decrease in apoptosis in H2O2-treated cardiomyocytes. Furthermore, FTX enhanced the expression of KLF13 protein through interaction with miR-150. Upregulation of FTX repressed apoptosis in I/R-injured heart tissues in vivo.ConclusionFTX relieves H2O2-induced cardiomyocyte injury by increasing KLF13 expression via depletion of miR-150, thus providing a novel therapeutic target for the alleviation of I/R injury.
Highlights
Acute myocardial infarction (AMI) is a serious cardiovascular disease accompanied with quadriplegia or paraplegia [1]
In order to investigate the effects of Five prime to Xist (FTX) on cell viability and apoptosis of H2O2-treated cardiomyocytes, untransfected or transfected H9C2 cells were treated with 100 μM H2O2 for 24 h
MiR-150 levels were decreased (Figure 8d), and Kruppel-like factor 13 (KLF13) levels increased (Figure 8e) in the transfected-FTX I/R group compared with the transfected-pcDNA I/R group. These results suggest that FTX upregulation represses apoptosis in cardiomyocytes by regulating the miR-150/KLF13 axis in an in vivo model of I/R
Summary
Acute myocardial infarction (AMI) is a serious cardiovascular disease accompanied with quadriplegia or paraplegia [1]. AMI pathogenesis is complicated and includes factors such as obesity, sedentary lifestyle, diabetes, smoking, and dyslipidemia. Myocardial reperfusion has dramatically improved the therapeutic outcomes of AMI patients [2,3]. Myocardial reperfusion can often lead to ischemia/reperfusion (I/R) injury and initiate oxidative stress, ventricular arrhythmias, cardiomyocyte death, and neuronal apoptosis [4,5,6]. Long noncoding RNAs (lncRNAs) are critical modulators of many diseases through their impact on gene expression [7]. LncRNA five prime to Xist (FTX), located at X-chromosome inactivation center, is associated with the pathogenesis of multiple diseases, such as epilepsy, heart disease, and cancers [8,9]. FTX acts as an oncogene to increase cell growth, This work is licensed under the Creative Commons Attribution 4.0
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