<scp>BCL</scp>‐6 promotes the methylation of <scp>miR</scp>‐34a by recruiting <scp>EZH2</scp> and upregulating <scp>CTRP9</scp> to protect ischemic myocardial injury

Lin, Jiunn-Miin; Hsu, Chih-Hsiang; Chen, Robert J.; Kao, Shao‐Hsuan; Lin, You-Cian

doi:10.1002/biof.1704

Cited by 16 publications

(10 citation statements)

References 30 publications

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“…In this regard, a recent study demonstrated that miR-34a was highly expressed in the heart tissue of AMI, which promoted cell apoptosis and oxidative stress. The results indicated that inhibition of miR-34a attenuated myocardial injury by multiple gene regulation of cellular phenotypes (69). Recent studies have shown that some mature miRs are also modified by m6A/m5C methylation, and that these modified mature miRs are significantly differentially expressed among cancer tissues (70).…”

Section: Roles Of Mir-34a In MI and Hfmentioning

confidence: 98%

“…Recent studies have shown that some mature miRs are also modified by m6A/m5C methylation, and that these modified mature miRs are significantly differentially expressed among cancer tissues (70). Similarly in the cardiovascular system, methylation of miR-34a promoted by Bcl-6 has a cardioprotective effect on AMI via the EZH2/miR-34a/CTRP9 axis (69). In the early stage of AMI, prevention of heart failure and left ventricular remodeling are closely related to the prognosis of patients, and left ventricular remodeling after AMI is associated with poor prognosis (68).…”

Section: Roles Of Mir-34a In MI and Hfmentioning

confidence: 99%

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Targeting the microRNA-34a as a Novel Therapeutic Strategy for Cardiovascular Diseases

Hua

Liu

Liang³

et al. 2022

Front. Cardiovasc. Med.

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Cardiovascular diseases (CVDs) are still the main cause of morbidity and mortality worldwide and include a group of disorders varying from vasculature, myocardium, arrhythmias and cardiac development. MicroRNAs (miRs) are endogenous non-coding RNAs with 18–23 nucleotides that regulate gene expression. The miR-34 family, including miR-34a/b/c, plays a vital role in the regulation of myocardial physiology and pathophysiological processes. Recently, miR-34a has been implicated in cardiovascular fibrosis, dysfunction and related cardiovascular disorders as an essential regulator. Interestingly, there is a pivotal link among miR-34a, cardiovascular fibrosis, and Smad4/TGF-β1 signaling. Notably, both loss-of-function and gain-of-function approaches identified the critical roles of miR-34a in cardiovascular apoptosis, autophagy, inflammation, senescence and remodeling by modulating multifunctional signaling pathways. In this article, we focus on the current understanding of miR-34a in biogenesis, its biological effects and its implications for cardiac pathologies including myocardial infarction, heart failure, ischaemia reperfusion injury, cardiomyopathy, atherosclerosis, hypertension and atrial fibrillation. Thus, further understanding of the effects of miR-34a on cardiovascular diseases will aid the development of effective interventions. Targeting for miR-34a has emerged as a potential therapeutic target for cardiovascular dysfunction and related diseases.

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Section: Roles Of Mir-34a In MI and Hfmentioning

confidence: 98%

Section: Roles Of Mir-34a In MI and Hfmentioning

confidence: 99%

Targeting the microRNA-34a as a Novel Therapeutic Strategy for Cardiovascular Diseases

Hua

Liu

Liang³

et al. 2022

Front. Cardiovasc. Med.

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“…The lncRNA NEAT1 recruits EZH2 to the Smad7 promoter, increases Smad7 methylation, and accelerates the development of heart failure and ventricular remodeling [ 175 ]. Also, EZH2 can promote the methylation level of mir-34a to inhibit the apoptosis of cardiomyocytes after acute myocardial infarction and improve myocardial injury [ 176 ]. In addition, lncRNA ANRIL is upregulated in patients with coronary atherosclerotic heart disease and promotes the binding of WDR5 (the key subunit of the HMT H3K4MT complex) to HDAC3 to form the WRD5–HDAC3 complex, which regulates oxidative stress and increases reactive oxygen species (ROS) levels [ 177 ].…”

Section: Regulatory Mechanisms Of Chromatin Modifiersmentioning

confidence: 99%

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms

Nie,

Song,

Huang

et al. 2024

Mol Biomed

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The field of transcriptional regulation has revealed the vital role of chromatin modifiers in human diseases from the beginning of functional exploration to the process of participating in many types of disease regulatory mechanisms. Chromatin modifiers are a class of enzymes that can catalyze the chemical conversion of pyrimidine residues or amino acid residues, including histone modifiers, DNA methyltransferases, and chromatin remodeling complexes. Chromatin modifiers assist in the formation of transcriptional regulatory circuits between transcription factors, enhancers, and promoters by regulating chromatin accessibility and the ability of transcription factors to acquire DNA. This is achieved by recruiting associated proteins and RNA polymerases. They modify the physical contact between cis-regulatory factor elements, transcription factors, and chromatin DNA to influence transcriptional regulatory processes. Then, abnormal chromatin perturbations can impair the homeostasis of organs, tissues, and cells, leading to diseases. The review offers a comprehensive elucidation on the function and regulatory mechanism of chromatin modifiers, thereby highlighting their indispensability in the development of diseases. Furthermore, this underscores the potential of chromatin modifiers as biomarkers, which may enable early disease diagnosis. With the aid of this paper, a deeper understanding of the role of chromatin modifiers in the pathogenesis of diseases can be gained, which could help in devising effective diagnostic and therapeutic interventions.

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“…15 In addition, BCL6 may play an important role in the pathophysiological process of ischemiahypoxic injury in cardiomyocytes and protect cardiomyocytes by inhibiting oxidative stress, inflammation, and cell apoptosis. 16,33,34 However, the regulatory mechanisms of BCL6 in cardiomyocytes are not fully understood. In this study, using the mouse heart failure model and the cardiomyocyte injury model, DDX17 was found to bind to BCL6 and jointly participate in inhibiting the expression of the downstream gene Drp1, which results in blocking the excessive fission of myocardial mitochondria and maintaining their homeostasis and function.…”

Section: Overexpression Of Ddx17 In Cardiomyocytes Reduces Myocardial...mentioning

confidence: 99%

DEAD-box helicase 17 (DDX17) protects cardiac function by promoting mitochondrial homeostasis in heart failure

Yan,

Gao,

Lan

et al. 2024

Sig Transduct Target Ther

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DEAD-box helicase 17 (DDX17) is a typical member of the DEAD-box family with transcriptional cofactor activity. Although DDX17 is abundantly expressed in the myocardium, its role in heart is not fully understood. We generated cardiomyocyte-specific Ddx17-knockout mice (Ddx17-cKO), cardiomyocyte-specific Ddx17 transgenic mice (Ddx17-Tg), and various models of cardiomyocyte injury and heart failure (HF). DDX17 is downregulated in the myocardium of mouse models of heart failure and cardiomyocyte injury. Cardiomyocyte-specific knockout of Ddx17 promotes autophagic flux blockage and cardiomyocyte apoptosis, leading to progressive cardiac dysfunction, maladaptive remodeling and progression to heart failure. Restoration of DDX17 expression in cardiomyocytes protects cardiac function under pathological conditions. Further studies showed that DDX17 can bind to the transcriptional repressor B-cell lymphoma 6 (BCL6) and inhibit the expression of dynamin-related protein 1 (DRP1). When DDX17 expression is reduced, transcriptional repression of BCL6 is attenuated, leading to increased DRP1 expression and mitochondrial fission, which in turn leads to impaired mitochondrial homeostasis and heart failure. We also investigated the correlation of DDX17 expression with cardiac function and DRP1 expression in myocardial biopsy samples from patients with heart failure. These findings suggest that DDX17 protects cardiac function by promoting mitochondrial homeostasis through the BCL6-DRP1 pathway in heart failure.

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BCL‐6 promotes the methylation of miR‐34a by recruiting EZH2 and upregulating CTRP9 to protect ischemic myocardial injury

Cited by 16 publications

References 30 publications

Targeting the microRNA-34a as a Novel Therapeutic Strategy for Cardiovascular Diseases

Targeting the microRNA-34a as a Novel Therapeutic Strategy for Cardiovascular Diseases

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms

DEAD-box helicase 17 (DDX17) protects cardiac function by promoting mitochondrial homeostasis in heart failure

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