The long noncoding RNA NRF regulates programmed necrosis and myocardial injury during ischemia and reperfusion by targeting miR-873

Wang, K.; Liu, F.; Liu, C. Y.; An, Tao; Zhang, J.; Zhou, Luqian; Wang, Mao-Hui; Dong, Yanhan; Li, N.; Gao, Jinling; Zhao, Yanfang; Li, Peifeng

doi:10.1038/cdd.2016.28

Cited by 192 publications

(146 citation statements)

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“…The heatmap of the mRNA microarray showed that RIPK1 was highly expressed in the I/R injury mouse model, which led us to hypothesize that we could inhibit RIPK1 expression and reduce myocardial I/R injury. The research of Wang K et al illustrated that RIPK1 was highly expressed in a myocardial ischemia/reperfusion injury mouse model, which is consistent with our results [13]. MicroRNA microarrays were re-analyzed to identify differentially expressed miRNAs.…”

Section: Discussionsupporting

confidence: 90%

“…It has been reported that cell survival or death can be regulated by several RIPK1-mediated pathways, such as the tumor necrosis factor (TNF) signaling pathway, which ultimately results in NF-κB expression and participation in the deoxyribonucleic acid (DNA) transcription process [12]. In addition to RIPK1, Ripk3 also participates in the regulation of necrotic death in particular cell types, and both RIPK1 and Ripk3 have been demonstrated to be activated in ischemic heart disease [13]. Oerlemans MI et al were the first to demonstrate that the phosphorylation of RIPK1 is increased in the heart after ischemia/reperfusion, and the suppression of RIPK1-dependent necrosis can inhibit adverse cardiac remodeling after I/R injury [14].…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-24-3p Attenuates Myocardial Ischemia/Reperfusion Injury by Suppressing RIPK1 Expression in Mice

Tan¹,

Qi²,

Fan³

et al. 2018

Cell Physiol Biochem

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Background/Aims: This study was developed to investigate a potential therapeutic method for myocardial ischemia/reperfusion injury involving the promotion of miR-24-3p expression. Methods: Microarray analysis was used to screen differentially expressed genes in a myocardial ischemia/reperfusion (I/R) injury mouse model. Gene set enrichment analysis was utilized to determine vital signaling pathways. Targeting verification was conducted with a luciferase reporter assay. Myocardial I/R injury was developed in mice, and the expression levels of RIPK1 and miR-24-3p were investigated by qRT-PCR and Western blot. Hemodynamic parameters and the activity of serum myocardial enzymes were measured to evaluate cardiac function. Infarct area was observed through HE and TTC staining. Myocardial cell apoptosis was examined by TUNEL staining and caspase-3 activity analysis. Results: RIPK1 was an upregulated mRNA found by microarray analysis and a verified target of the downregulated miRNA miR-24-3p. The upregulation of RIPK1 (1.8-fold) and the downregulation of miR-24-3p (0.3-fold) were confirmed in I/R mice. RIPK1 led to impaired cardiac function indexes, increased infarct area and cell apoptosis, while miR-24-3p could reverse the injury by regulating RIPK1. The TNF signaling pathway was proven to be involved in myocardial I/R injury through the detection of the dysregulation of related proteins. Conclusion: In conclusion, RIPK1 was upregulated and miR-24-3p was downregulated in a myocardial I/R injury mouse model. RIPK1 could aggravate myocardial I/R injury via the TNF signaling pathway, while miR-24-3p could suppress RIPK1 and therefore exert cardioprotective effects in myocardial I/R injury.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

MicroRNA-24-3p Attenuates Myocardial Ischemia/Reperfusion Injury by Suppressing RIPK1 Expression in Mice

Tan¹,

Qi²,

Fan³

et al. 2018

Cell Physiol Biochem

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“…Myocytes injured during heart disease include both apoptotic and necrotic cells. Studies have shown that necrosis is more prominent in failing hearts and I/R hearts, which indicated that necrosis plays an important role in the pathological process of cardiac disease [11][12][13][14][15][16][17]. Oxidative stress is defined as an excess production of reactive oxygen species (ROS) relative to the endogenous antioxidant reserve to counteract the effects of ROS [18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

FGF-2 Transcriptionally Down-Regulates the Expression of BNIP3L via PI3K/Akt/FoxO3a Signaling and Inhibits Necrosis and Mitochondrial Dysfunction Induced by High Concentrations of Hydrogen Peroxide in H9c2 Cells

Chen

Han

et al. 2016

Cell Physiol Biochem

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Background/Aims: Cardiovascular disease is a growing major global public health problem. Necrosis is one of the main forms of cardiomyocyte death in heart disease. Oxidative stress is regarded as one of the key regulators of cardiac necrosis, which eventually leads to cardiovascular disease. Many pharmacological and in vitro studies have suggested that FGF-2 can act directly on cardiomyocytes to maintain the integrity and function of the myocardium and prevent damage during oxidative stress. However, the mechanisms by which FGF-2 rescues the myocardium from oxidative stress damage in cardiovascular disease remain unclear. The present study explored the protective effects of FGF-2 in the H₂O₂-induced necrosis of H9C2 cardiomyocytes as well as the possible signaling pathways involved. Methods: Necrosis of H9c2 cardiomyocytes was induced by H₂O₂ and assessed using a Cell Counting Kit-8 (CCK8) assay and flow cytometry analysis. The cells were pretreated with the PI3K/Akt inhibitor Wortmannin to investigate the possible involvement of the PI3K/Akt pathway in the protection by FGF-2. The levels of Akt, p-Akt, FoxO3a, p-FoxO3a, and BNIP3L were detected by Western blot. Chromatin immuno-precipitation (ChIP) analysis was used to test whether FoxO3a binds directly to the BNIP3L promoter region. A luciferase assay was used to study the effects of FoxO3a on BNIP3L gene promoter activity. Mitochondrial ΔΨM was quantified using tetramethylrhodamine methyl ester perchlorate (TMRM). The mitochondrial oxygen consumption rate (OCR) was assessed with a Seahorse XF24 Analyzer. Results: Treatment with H₂O₂ decreased the phosphorylation of Akt and FoxO3a, and it induced the nuclear localization of FoxO3a and the necrosis of H9c2 cells. These effects of H₂O₂ were abrogated by pretreatment with FGF-2. Furthermore, the protective effects of FGF-2 were abolished by the PI3K/Akt inhibitor Wortmannin. ChIP analyses indicated that FoxO3a binds directly to the BNIP3L promoter region. Using a luciferase assay, we further observed that FoxO3a increased BNIP3L gene promoter activity. As expected, overexpression of BNIP3L in H9C2 cardiomyoblast cells reduced the cardioprotection of FGF-2 in H₂O₂-induced necrosis and mitochondrial dysfunction. Conclusions: The present data suggest that FGF-2 protects against H₂O₂-induced necrosis of H9C2 cardiomyocytes via the activation of the PI3K/Akt/FoxO3a pathway. Moreover, the present results demonstrate that FoxO3a is an important transcription factor that acts by binding to the promoter and promoting the transcription of BNIP3L, and it contributes to the necrosis and mitochondrial dysfunction induced by H₂O₂ in H9c2 cardiomyoblast cells.

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“…MicorRNA‐873 was found to participate in the regulation of cardiomyocyte necrosis by targeting RIP1/RIP3. In that work, they found that the long noncoding RNA NRF could regulate necrosis by targeting microRNA‐873 77. Specifically, Wang found that microRNA‐103/107 regulated programmed necrosis and myocardial ischaemia/reperfusion injury through targeting FADD.…”

Section: Necrosis In Heart Diseasesmentioning

confidence: 98%

Molecular mechanism and therapy application of necrosis during myocardial injury

Ding

Tariq

et al. 2018

J Cellular Molecular Medi

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Necrosis is an ancient topic which gains new attraction in the research area these years. There is no doubt that some necrosis can be regulated by genetic manipulation other than an accidental cell death resulting from physical or chemical stimuli. Recent advances in the molecular mechanism underlying the programmed necrosis show a fine regulation network which indicates new therapy targets in human diseases. Heart diseases seriously endanger our health and have high fatality rates in the patients. Cell death of cardiac myocytes is believed to be critical in the pathogenesis of heart diseases. Although necrosis is likely to play a more important role in cardiac cell death than apoptosis, apoptosis has been paid much attention in the past 30 years because it used to be considered as the only form of programmed cell death. However, recent findings of programmed necrosis and the related signalling pathways have broadened our horizon in the field of programmed cell death and promote new pharmacological application in the treatment of heart diseases. In this review, we summarize the advanced progress in these signalling pathways and discuss the pathos‐physiological relevance and therapeutic implication of targeting necrosis in heart diseases treatment.

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The long noncoding RNA NRF regulates programmed necrosis and myocardial injury during ischemia and reperfusion by targeting miR-873

Cited by 192 publications

References 70 publications

MicroRNA-24-3p Attenuates Myocardial Ischemia/Reperfusion Injury by Suppressing RIPK1 Expression in Mice

MicroRNA-24-3p Attenuates Myocardial Ischemia/Reperfusion Injury by Suppressing RIPK1 Expression in Mice

FGF-2 Transcriptionally Down-Regulates the Expression of BNIP3L via PI3K/Akt/FoxO3a Signaling and Inhibits Necrosis and Mitochondrial Dysfunction Induced by High Concentrations of Hydrogen Peroxide in H9c2 Cells

Molecular mechanism and therapy application of necrosis during myocardial injury

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