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The role of Abraxas 2 (ABRO1 or KIAA0157), a component of the lysine63-linked deubiquitinating system, in the cardiomyocyte proliferation and myocardial regeneration is unknown. Here, we found that ABRO1 regulates cardiomyocyte proliferation and cardiac regeneration in the postnatal heart by targeting METTL3-mediated m6A methylation of Psph mRNA. The deletion of ABRO1 increased cardiomyocyte proliferation in hearts and restored the heart function after myocardial injury. On the contrary, ABRO1 overexpression significantly inhibited the neonatal cardiomyocyte proliferation and cardiac regeneration in mouse hearts. The mechanism by which ABRO1 regulates cardiomyocyte proliferation mainly involved METTL3-mediated Psph mRNA methylation and CDK2 phosphorylation. In the early postnatal period, METTL3-dependent m6A methylation promotes cardiomyocyte proliferation by hypermethylation of Psph mRNA and upregulating PSPH expression. PSPH dephosphorylates cyclin-dependent kinase 2 (CDK2), a positive regulator of cell cycle, at Thr14/Tyr15 and increases its activity. Upregulation of ABRO1 restricts METTL3 activity and halts the cardiomyocyte proliferation in the postnatal hearts. Thus, our study reveals that ABRO1 is an essential contributor in the cell cycle withdrawal and attenuation of proliferative response in the postnatal cardiomyocytes and could act as a potential target to accelerate cardiomyocyte proliferation and cardiac repair in the adult heart.
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Miocárdio , Miócitos Cardíacos , Proteínas Associadas à Matriz Nuclear , Monoéster Fosfórico Hidrolases , Animais , Camundongos , Animais Recém-Nascidos , Proliferação de Células , Coração/fisiologia , Miócitos Cardíacos/metabolismo , RNA Mensageiro/metabolismo , Proteínas Associadas à Matriz Nuclear/metabolismo , Monoéster Fosfórico Hidrolases/metabolismoRESUMO
INTRODUCTION: There are many migrant workers in China's first-tier cities, but little is known about road safety. This paper systematically analysed road traffic injuries and risk factors among migrant workers in Guangzhou, China. METHODS: Road traffic crash data from 2017 to 2021 were obtained from the Guangzhou Public Security Traffic Management Integrated System. We plotted the crash network of road users in road traffic crashes and used logistic regression to analyse the risk factors for migrant workers of motorcycle and four-wheeled vehicle crashes. Moreover, the roles of migrant workers and control individuals as perpetrators in road traffic crashes were also analysed. RESULTS: Between 2017 and 2021, 76% of road traffic injuries were migrant workers in Guangzhou. Migrant workers who were motorcyclist drivers most commonly experienced road traffic injuries. Crashes between motorcyclists and car occupants were the most common. The illegal behaviours of migrant worker motorcyclists were closely related to casualties, with driving without a licence only and driving without a licence and drunk driving accounting for the greatest number. Migrant workers were responsible for many injuries of other road users. Motorcycle drivers have a higher proportion of drunk driving. DISCUSSION: Migrant workers play an important role in road traffic safety. They were both the leading source of road traffic injuries and the main perpetrators of road traffic crashes. Measures such as strict requirements for migrant workers to drive motorcycles with licences, prohibit drunk driving, greater publicity of road safety regulations, and combining compulsory education with punishment for illegal behaviours.
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Acidentes de Trânsito , Motocicletas , Migrantes , Humanos , Acidentes de Trânsito/estatística & dados numéricos , China/epidemiologia , Migrantes/estatística & dados numéricos , Masculino , Feminino , Adulto , Fatores de Risco , Motocicletas/estatística & dados numéricos , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/prevenção & controle , Condução de Veículo/estatística & dados numéricos , Condução de Veículo/legislação & jurisprudência , Dirigir sob a Influência/estatística & dados numéricos , Dirigir sob a Influência/legislação & jurisprudência , Pessoa de Meia-IdadeRESUMO
Circular RNAs (circRNAs), a novel class of endogenous noncoding RNA, are characterized by their covalently closed-loop structures without a 5' cap or a 3' poly(A) tail. With the evolution of high-throughput sequencing technology and bioinformatics, an increasing number of circRNAs have been discovered, and their functions were highlighted. Cardiovascular diseases (CVDs) have become the world's leading killers, with serious impacts on human health. Although significant progress has been made in clarifying the development of CVDs from the molecular to the cellular level, CVDs remain one of the leading causes of death in humans. circRNAs mainly function as a "sponge" to absorb microRNAs, which results in the positive control of downstream proteins. They play important regulatory roles in the development of CVDs. This paper reviews current knowledge on the biogenesis, detection and validation, translation, translocation and degradation, and general functions of circRNAs, with a focus on their roles in CVDs.
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Doenças Cardiovasculares , RNA Circular , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/terapia , Biologia Computacional , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismoRESUMO
PIWI-interacting RNAs (piRNAs) are recently discovered small non-coding RNAs consisting of 24-35 nucleotides, usually including a characteristic 5-terminal uridine and an adenosine at position 10. PIWI proteins can specifically bind to the unique structure of the 3' end of piRNAs. In the past, it was thought that piRNAs existed only in the reproductive system, but recently, it was reported that piRNAs are also expressed in several other human tissues with tissue specificity. Growing evidence shows that piRNAs and PIWI proteins are abnormally expressed in various diseases, including cancers, neurodegenerative diseases and ageing, and may be potential biomarkers and therapeutic targets. This review aims to discuss the current research status regarding piRNA biogenetic processes, functions, mechanisms and emerging roles in various diseases.
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Envelhecimento , Neoplasias/patologia , Doenças Neurodegenerativas/patologia , RNA Interferente Pequeno/genética , Animais , Epigênese Genética , Humanos , Neoplasias/genética , Doenças Neurodegenerativas/genéticaRESUMO
Gastric cancer (GC) is one of the most common malignant tumours in the world and has high morbidity and mortality. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently linked circular structures. In recent years, plentiful circRNAs have been discovered that participate in many biological processes, including the initiation and development of tumours. Increasing evidences suggest important biological functions of circRNAs, implying that circRNAs may serve as vital new biomarkers and targets for disease diagnosis and prognosis. Among these, circRNAs are tend to aberrantly expressed and are regarded as potential biomarkers in the carcinogenesis and progression of GC. This review systematically summarised the biogenesis, biological properties and functions of circRNAs, with a focus on their relationship with GC, as well as their probable clinical implications on GC. As our cognition of the relation between circRNAs and GC deepens, more molecular mechanisms of GC progression will be discovered, and new therapeutic strategies will be used for the prevention and treatment of GC.
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Biomarcadores Tumorais , Estudos de Associação Genética , Predisposição Genética para Doença , RNA Circular , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Transcrição Gênica , Animais , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs , Prognóstico , Splicing de RNA , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidadeRESUMO
OBJECTIVE: This article reports two accidents caused by defective Takata airbags ruptured, which led to the deaths of the drivers. This is the first public report on the deaths caused by Takata airbags in China. METHODS: Determine the relationship between the driver death and airbag rupture through autopsy indings and vehicle inspection. RESULTS: Due to defects in the design of Takata's inflator, moist air was permitted to slowly enter the inflator, resulting the PSAN slowly degraded physically. The damaged propellant burned more rapidly than intended and overpressurized the inflator's steel housing, causing fragmentation and flying debris at high speed, killing or injuring vehicle occupants. CONCLUSIONS: To date, there are still tens of millions of defective Takata airbags that have not been recalled for repair, posing safety risks. This article suggests taking preventive measures to avoid the occurrence of similar accidents.
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Air Bags , Humanos , Air Bags/efeitos adversos , Acidentes de Trânsito , Autopsia , ChinaRESUMO
Histone lysine crotonylation (Kcr) is a new acylation modification first discovered in 2011, which has important biological significance for gene expression, cell development, and disease treatment. In the past over ten years, numerous signs of progress have been made in the research on the biochemistry of Kcr modification, especially a series of Kcr modification-related "reader", "eraser", and "writer" enzyme systems are identified. The physiological function of crotonylation and its correlation with development, heredity, and spermatogenesis have been paid more and more attention. However, the development of disease is usually associated with abnormal Kcr modification. In this review, we summarized the identification of crotonylation modification, Kcr-related enzyme system, biological functions, and diseases caused by abnormal Kcr. This knowledge supplies a theoretical basis for further exploring the function of crotonylation in the future.
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Introduction: Electric bicycles (e-bikes) and bicycles in large Chinese cities have recently witnessed substantial growth in ridership. According to related accident trends, this study analyzed characteristics and spatial distribution in the period when e-bike-related accidents rapidly increased to propose priority measures to reduce accident casualties. Methods: For e-bike- and bicycle-related accident data from the Guangzhou Public Security Traffic Management Integrated System, linear regression was used to examine the trends in the number of accidents and age-adjusted road traffic casualties from 2011 to 2021. Then, for the period when e-bike-related accidents rapidly increased, descriptive statistics were computed regarding rider characteristics, illegal behaviors, road types, collision objects and their accident liability. One-way analysis of variance (ANOVA) followed by Bonferroni's multiple comparison test. P < 0.05 was considered statistically significant. Finally, the density distribution of accidents was presented, and Moran's I (MI) was used for assessing spatial autocorrelation. Hotspots were identified based on an optimized hotspot analysis tool. Results: Between 2011 and 2021, the number of accidents and casualty rate (per 100,000 population) increased for e-bikes but decreased for bicycles. After 2018, e-bike-related accidents increased rapidly, and bicycle-related accidents plateaued. Accident hotspots were concentrated in central city areas and suburban areas close to the former. Three-quarters of accidents occurred in motorized vehicle lanes. Most occurred on roads without physically segregated nonmotorized vehicle lanes. More than three-fifths of the accidents involved motor vehicles with at least four wheels. The prevalence (per 100 people) of casualties among e-bike rider victims and cyclist victims accounted for 92.0 % and 96.5 %, respectively. A total of 71.6 % of e-bike-related accidents involved migrant workers. Riding in motorized vehicle lanes was the most common illegal behavior. Conclusions: Although e-bike-related and bicycle-related accidents presented similar characteristics, the sharp increase in e-bike-related accidents requires attention. To improve e-bike safety, governments should develop appropriate countermeasures to prevent riders from riding on motorways, such as improving road infrastructure, adjusting the driver's license system and addressing priority control areas.
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Excessive death of myocardial cells can lead to various cardiovascular diseases and even develop into heart failure, so developing ideal treatment plans based on pathogenesis is of great significance for cardiopathy. After the heart undergoes ischemiaâreperfusion (I/R), myocardial cells accumulate a large amount of peroxides, leading to mitochondrial dysfunction and inducing ferroptosis. Ferroptosis is a form of iron-dependent regulatory cell death (RCD) caused by imbalanced redox and iron metabolism that leads to severe cell damage through the accumulation of peroxides. The mechanism of ferroptosis is highly correlated with mitochondrial metabolism. Myocardial cells are rich in a large number of mitochondria, which serve as energy supply centers and are prone to producing reactive oxygen species (ROS), providing opportunities for oxidative stress caused by ferroptosis. Ferroptosis is related to various cardiovascular diseases, and potential treatment methods designed around ferroptosis may alter the pathological progression of cardiovascular diseases. Therefore, this review investigates the regulatory mechanisms of ferroptosis, exploring the close pathological and physiological connections between ferroptosis and mitochondrial and cardiac I/R injury. Targeting ferroptosis and mitochondria for intervention may be an effective plan for preventing and treating cardiac I/R injury.
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Doenças Cardiovasculares , Ferroptose , Traumatismo por Reperfusão , Humanos , Doenças Cardiovasculares/metabolismo , Traumatismo por Reperfusão/metabolismo , Ferro/metabolismo , Mitocôndrias/metabolismo , Peróxidos/metabolismoRESUMO
The Cre-loxP-mediated genetic lineage tracing system is essential for constructing the fate mapping of single-cell progeny or cell populations. Understanding the structural hierarchy of cardiac progenitor cells facilitates unraveling cell fate and origin issues in cardiac development. Several prospective Cre-loxP-based lineage-tracing systems have been used to analyze precisely the fate determination and developmental characteristics of endocardial cells (ECs), epicardial cells, and cardiomyocytes. Therefore, emerging lineage-tracing techniques advance the study of cardiovascular-related cellular plasticity. In this review, we illustrate the principles and methods of the emerging Cre-loxP-based genetic lineage tracing technology for trajectory monitoring of distinct cell lineages in the heart. The comprehensive demonstration of the differentiation process of single-cell progeny using genetic lineage tracing technology has made outstanding contributions to cardiac development and homeostasis, providing new therapeutic strategies for tissue regeneration in congenital and cardiovascular diseases (CVDs).
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Introduction: This study aimed to explore the trend and main influencing factors of road traffic accidents in Guangzhou, China, from 2007 to 2020 and to provide a reference and guidance for government decision-making. Methods: A retrospective cohort study was used to describe road traffic accidents in Guangzhou. According to the population types, all people with road traffic accidents were divided into migrant workers and the control population. We divided road users, administrative districts, motorcycle types and injury levels into subgroups to investigate the characteristics of road traffic accidents in Guangzhou. The road traffic accident data were derived from the Guangzhou Public Security Traffic Management Integrated System. Results: The incidence rate of road traffic accidents per 10,000 vehicles in Guangzhou decreased from 36.55 in 2007 to 10.07 in 2012, remained relatively stable at 9.47 in 2017, and finally rose to 11.12 in 2020. The injury rate showed the same trend as the incidence rate, while the mortality rate gradually decreased from 14.21 in 2007 to 5.19 in 2020. Vulnerable road users such as motorized two-to-three-wheeler drivers and migrant workers were casualties in more than 80% of the cases. The proportion of casualties involving mopeds and electric bicycles increased rapidly after 2018. Motor vehicle drivers frequently caused road traffic accidents and were most often uninjured. Conclusion: Road safety in Guangzhou has shown a clear trend of improvement, but casualties are uneven across administrative districts. More attention should be given to motorized two-to-three-wheelers, migrant workers, and road traffic violations by uninjured individuals.
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The mitochondrial transmembrane (TMEM) protein family has several essential physiological functions. However, its roles in cardiomyocyte proliferation and cardiac regeneration remain unclear. Here, we detected that TMEM11 inhibits cardiomyocyte proliferation and cardiac regeneration in vitro. TMEM11 deletion enhanced cardiomyocyte proliferation and restored heart function after myocardial injury. In contrast, TMEM11-overexpression inhibited neonatal cardiomyocyte proliferation and regeneration in mouse hearts. TMEM11 directly interacted with METTL1 and enhanced m7G methylation of Atf5 mRNA, thereby increasing ATF5 expression. A TMEM11-dependent increase in ATF5 promoted the transcription of Inca1, an inhibitor of cyclin-dependent kinase interacting with cyclin A1, which suppressed cardiomyocyte proliferation. Hence, our findings revealed that TMEM11-mediated m7G methylation is involved in the regulation of cardiomyocyte proliferation, and targeting the TMEM11-METTL1-ATF5-INCA1 axis may serve as a novel therapeutic strategy for promoting cardiac repair and regeneration.
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Miócitos Cardíacos , Processamento de Proteína Pós-Traducional , Animais , Camundongos , Proliferação de Células/genética , Metilação , Miócitos Cardíacos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
PIWI-interacting RNAs (piRNAs) are highly expressed in various cardiovascular diseases. However, their role in cardiomyocyte death caused by ischemia/reperfusion (I/R) injury, especially necroptosis, remains elusive. In this study, a heart necroptosis-associated piRNA (HNEAP) is found that regulates cardiomyocyte necroptosis by targeting DNA methyltransferase 1 (DNMT1)-mediated 5-methylcytosine (m5 C) methylation of the activating transcription factor 7 (Atf7) mRNA transcript. HNEAP expression level is significantly elevated in hypoxia/reoxygenation (H/R)-exposed cardiomyocytes and I/R-injured mouse hearts. Loss of HNEAP inhibited cardiomyocyte necroptosis and ameliorated cardiac function in mice. Mechanistically, HNEAP directly interacts with DNMT1 and attenuates m5 C methylation of the Atf7 mRNA transcript, which increases Atf7 expression level. ATF7 can further downregulate the transcription of Chmp2a, an inhibitor of necroptosis, resulting in the reduction of Chmp2a level and the progression of cardiomyocyte necroptosis. The findings reveal that piRNA-mediated m5 C methylation is involved in the regulation of cardiomyocyte necroptosis. Thus, the HNEAP-DNMT1-ATF7-CHMP2A axis may be a potential target for attenuating cardiac injury caused by necroptosis in ischemic heart disease.
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Miócitos Cardíacos , Traumatismo por Reperfusão , Camundongos , Animais , Miócitos Cardíacos/metabolismo , RNA Mensageiro/metabolismo , RNA de Interação com Piwi , Necroptose/genética , Metilação , Traumatismo por Reperfusão/metabolismo , Fatores Ativadores da Transcrição/metabolismoRESUMO
Cardiovascular disease (CVD) is a common disease that poses a huge threat to human health. Irreversible cardiac damage due to cardiomyocyte death and lack of regenerative capacity under stressful conditions, ultimately leading to impaired cardiac function, is the leading cause of death worldwide. The regulation of cardiomyocyte death plays a crucial role in CVD. Previous studies have shown that the modes of cardiomyocyte death include apoptosis and necrosis. However, another new form of death, pyroptosis, plays an important role in CVD pathogenesis. Pyroptosis induces the amplification of inflammatory response, increases myocardial infarct size, and accelerates the occurrence of cardiovascular disease, and the control of cardiomyocyte pyroptosis holds great promise for the treatment of cardiovascular disease. In this paper, we summarized the characteristics, occurrence and regulation mechanism of pyroptosis are reviewed, and also discussed its role and mechanisms in CVD, such as atherosclerosis (AS), myocardial infarction (MI), arrhythmia and cardiac hypertrophy.
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The dietary flavonoid quercetin is ubiquitously distributed in fruits, vegetables, and medicinal herbs. Quercetin has been a focal point in recent years due to its versatile health-promoting benefits and high pharmacological values. It has well documented that quercetin exerts anticancer actions by inhibiting cell proliferation, inducing apoptosis, and retarding the invasion and metastasis of cancer cells. However, the exact mechanism of quercetin-mediated cancer chemoprevention is still not fully understood. With the advances in high-throughput sequencing technologies, the intricate oncogenic signaling networks have been gradually characterized. Increasing evidence on the close association between noncoding RNA (ncRNAs) and cancer etiopathogenesis emphasizes the potential of ncRNAs as promising molecular targets for cancer treatment. Available experimental studies indicate that quercetin can dominate multiple cancer-associated ncRNAs, hence repressing carcinogenesis and cancer development. Thus, modulation of ncRNAs serves as a key mechanism responsible for the anticancer effects of quercetin. In this review, we focus on the chemopreventive effects of quercetin on cancer pathogenesis by targeting cancer-relevant ncRNAs, supporting the viewpoint that quercetin holds promise as a drug candidate for cancer chemoprevention and chemotherapy. An in-depth comprehension of the interplay between quercetin and ncRNAs in the inhibition of cancer development and progression will raise the possibility of developing this bioactive compound as an anticancer agent that could be highly efficacious and safe in clinical practice.
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Antineoplásicos , Neoplasias , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , Quercetina/farmacologia , Quercetina/uso terapêutico , RNA não Traduzido/genéticaRESUMO
Lung cancer (LC) is a commonly diagnosed cancer with an unsatisfactory prognosis. Extracellular vesicles (EVs) are lipid bilayer-delimited particles that mediate cell-cell communication by transporting various biomacromolecules, such as nucleic acids, proteins, and lipids. Noncoding RNAs (ncRNAs), including microRNAs, circular RNAs, and long noncoding RNAs, are important noncoding transcripts that play critical roles in a variety of physiological and pathological processes, especially in cancer. ncRNAs have been verified to be packaged into EVs and transported between LC cells and stromal cells, regulating multiple LC malignant phenotypes, such as proliferation, migration, invasion, epithelial-mesenchymal transition, metastasis, and treatment resistance. Additionally, EVs can be detected in various body fluids and are associated with the stage, grade, and metastasis of LC. Herein, we summarize the biological characteristics and functions of EV ncRNAs in the biological processes of LC, focusing on their potential to serve as diagnostic and prognostic biomarkers of LC as well as their probable role in the clinical treatment of LC. EV ncRNAs provide a new perspective for understanding the mechanism underlying LC pathogenesis and development, which might benefit numerous LC patients in the future.
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The mechanism of cardiovascular diseases (CVDs) is complex and threatens human health. Cardiomyocyte death is an important participant in the pathophysiological basis of CVDs. Ferroptosis is a new type of iron-dependent programmed cell death caused by excessive accumulation of iron-dependent lipid peroxides and reactive oxygen species (ROS) and abnormal iron metabolism. Ferroptosis differs from other known cell death pathways, such as apoptosis, necrosis, necroptosis, autophagy and pyroptosis. Several compounds have been shown to induce or inhibit ferroptosis by regulating related key factors or signalling pathways. Recent studies have confirmed that ferroptosis is associated with the development of diverse CVDs and may be a potential therapeutic drug target for CVDs. In this review, we summarize the characteristics and related mechanisms of ferroptosis and focus on its role in CVDs, with the goal of inspiring novel treatment strategies.
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Doxorubicin (DOX) is an efficacious and widely used drug for human malignancy treatment, but its clinical application is limited due to side effects, especially cardiotoxicity. Our present study revealed that DOX could induce apoptosis in cardiomyocytes. Herein, we screened the dysregulated long noncoding RNAs (lncRNAs) in DOX-treated cardiomyocytes. Notably, overexpression of lncRNA NONMMUT015745 (lnc5745) could alleviate DOX-induced cardiomyocyte apoptosis both in vitro and in vivo. Conversely, silencing lnc5745 promotes cardiomyocyte apoptosis. Moreover, Rab2A, a direct target of lnc5745, possesses a protective effect in DOX-induced cardiotoxicity once knocked down. Importantly, we verified that the p53-related apoptotic signalling pathway was responsible for the lnc5745-mediated protective role against DOX-induced cardiomyocyte apoptosis. Mechanistically, Rab2A interacts with p53 and phosphorylated p53 on Ser 33 (p53 (Phospho-Ser 33)), promotes p53 phosphorylation, thereby activating the apoptotic pathway. Taken together, our results suggested that lnc5745 protects against DOX-induced cardiomyocyte apoptosis through suppressing Rab2A expression, modifying p53 phosphorylation, thereby regulating p53-related apoptotic signalling pathway. Our findings establish the functional mode of the lnc5745-Rab2A-p53 axis in DOX-induced cardiotoxicity. The development of new strategies targeting the lnc5745-Rab2A-p53 axis could attenuate DOX-induced cardiotoxicity, which is beneficial to its clinical anti-tumour application.
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Circular RNAs (circRNAs) are differentially expressed in various cardiovascular disease including myocardial ischemia-reperfusion (I/R) injury. However, their functional impact on cardiomyocyte cell death, in particular, in necrotic forms of death remains elusive. In this study, we found that the level of mmu_circ_000338, a cardiac- necroptosis-associated circRNA (CNEACR), was reduced in hypoxia-reoxygenation (H/R) exposed cardiomyocytes and I/R-injured mice hearts. The enforced expression of CNEACR attenuated the necrotic form of cardiomyocyte death caused by H/R and suppressed of myocardial necrosis in I/R injured mouse heart, which was accompanied by a marked reduction of myocardial infarction size and improved cardiac function. Mechanistically, CNEACR directly binds to histone deacetylase (HDAC7) in the cytoplasm and interferes its nuclear entry. This leads to attenuation of HDAC7-dependent suppression of forkhead box protein A2 (Foxa2) transcription, which can repress receptor-interacting protein kinase 3 (Ripk3) gene by binding to its promoter region. In addition, CNEACR-mediated upregulation of FOXA2 inhibited RIPK3-dependent necrotic/necroptotic death of cardiomyocytes. Our study reveals that circRNAs such as CNEACR can regulate the cardiomyocyte necroptosis associated activity of HDACs, promotes cell survival and improves cardiac function in I/R-injured heart. Hence, the CNEACR/HDAC7/Foxa2/ RIPK3 axis could be an efficient target for alleviating myocardial damage caused by necroptotic death in ischemia heart diseases.
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Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Animais , Fator 3-beta Nuclear de Hepatócito/metabolismo , Camundongos , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo , Necroptose , RNA Circular/genéticaRESUMO
PIWI-interacting RNAs (piRNAs) are abundantly expressed in heart. However, their functions and molecular mechanisms during myocardial infarction remain unknown. Here, a heart-apoptosis-associated piRNA (HAAPIR), which regulates cardiomyocyte apoptosis by targeting N-acetyltransferase 10 (NAT10)-mediated N4-acetylcytidine (ac4 C) acetylation of transcription factor EC (Tfec) mRNA transcript, is identified. HAAPIR deletion attenuates ischemia/reperfusion induced myocardial infarction and ameliorate cardiac function compared to WT mice. Mechanistically, HAAPIR directly interacts with NAT10 and enhances ac4 C acetylation of Tfec mRNA transcript, which increases Tfec expression. TFEC can further upregulate the transcription of BCL2-interacting killer (Bik), a pro-apoptotic factor, which results in the accumulation of Bik and progression of cardiomyocyte apoptosis. The findings reveal that piRNA-mediated ac4 C acetylation mechanism is involved in the regulation of cardiomyocyte apoptosis. HAAPIR-NAT10-TFEC-BIK signaling axis can be potential target for the reduction of myocardial injury caused by cardiomyocyte apoptosis in ischemia heart diseases.