Role of N6-Methyladenosine RNA Modification in Cardiovascular Disease

Song, Dandan; Hou, Jian; Wu, Junduo; Wang, Junnan

doi:10.3389/fcvm.2021.659628

Cited by 4 publications

(5 citation statements)

References 129 publications

(187 reference statements)

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“…For example, Let-7, miR-126, miR-143-3p and miR-221/222 can affect the function of endothelial cells and vascular smooth muscle cells in angiogenesis. Let-7, miR-25 and miR-375 have been proved to play key roles in the pathogenesis of a variety of cardiovascular diseases, and participate in the regulation of apoptosis, autophagy, oxidative stress, inflammatory response and calcium treatment, so as to participate in the occurrence of heart failure (88)(89)(90)(91). Therefore, the study of m6A methylation of these molecules is particularly important, which may help to further explore the pathogenesis of heart failure.…”

Section: M6a Methylation and Inflammatory Responsementioning

confidence: 99%

Role of m6A Methylation in the Occurrence and Development of Heart Failure

Fan

2022

Front. Cardiovasc. Med.

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N6-methyladenosine (m6A) RNA methylation is one of the most common epigenetic modifications in RNA nucleotides. It is known that m6A methylation is involved in regulation, including gene expression, homeostasis, mRNA stability and other biological processes, affecting metabolism and a variety of biochemical regulation processes, and affecting the occurrence and development of a variety of diseases. Cardiovascular disease has high morbidity, disability rate and mortality in the world, of which heart failure is the final stage. Deeper understanding of the potential molecular mechanism of heart failure and exploring more effective treatment strategies will bring good news to the sick population. At present, m6A methylation is the latest research direction, which reveals some potential links between epigenetics and pathogenesis of heart failure. And m6A methylation will bring new directions and ideas for the prevention, diagnosis and treatment of heart failure. The purpose of this paper is to review the physiological and pathological mechanisms of m6A methylation that may be involved in cardiac remodeling in heart failure, so as to explain the possible role of m6A methylation in the occurrence and development of heart failure. And we hope to help m6A methylation obtain more in-depth research in the occurrence and development of heart failure.

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Section: M6a Methylation and Inflammatory Responsementioning

confidence: 99%

Role of m6A Methylation in the Occurrence and Development of Heart Failure

Fan

2022

Front. Cardiovasc. Med.

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“…Recent research has shown that RNA methylation has a significant role in the development of CVDs. 128 METTL3 influences cardiac remodeling and hypertrophy via controlling cardiomyocyte and vascular smooth muscle cell differentiation as well as cardiomyocyte death, 9,129,130 whereas FTO inhibits cardiac remodeling and improves myocardial contractile function following myocardial infarction. 131 Although RNA alterations have been discovered to have a function in tumor and certain autoimmune illnesses by regulating immune responses, it is yet unknown if RNA modifications also play a role in CVDs by regulating immune inflammatory responses, and more research is needed.…”

Section: Implications Of Rna Methylation In Cardiovascular Diseasesmentioning

confidence: 99%

“…Recent research has shown that RNA methylation has a significant role in the development of CVDs 128 . METTL3 influences cardiac remodeling and hypertrophy via controlling cardiomyocyte and vascular smooth muscle cell differentiation as well as cardiomyocyte death, 9,129,130 whereas FTO inhibits cardiac remodeling and improves myocardial contractile function following myocardial infarction 131 .…”

Section: Implications Of Rna Methylation For Immunotherapymentioning

confidence: 99%

The effects of RNA methylation on immune cells development and function

2022

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Among the more than 170 known RNA modifications, methylation modification is the most frequent and well‐studied. Depending on where the methylation occurs, RNA methylation can be classified as N6‐methyladenosine, N1‐methyladenosine, 5‐methylcytosine, N7‐methylguanosine, and others. The methylation of RNA is constantly and dynamically modified in the complex microenvironment by methyltransferases, demethylases, and methylation reading proteins. These changes affect the proliferation and differentiation of immune cells as well as their effector activities by affecting RNA location, activity, stability, and translation efficiency. This review outlines how diverse RNA methylation alterations affect immune cell development and biological activity, as well as the role of RNA methylation in health and disease, to provide a molecular basis for future immunotherapies.

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“…The most studied m 6 A readers are the YT521‐B homology (YTH) domain family, including YTHDF1/2/3 and YTHDC1/2, which perform recognition functions for RNA modifications (Bai et al, 2019; Shi et al, 2017b). Recent and compelling evidence indicates that m 6 A is one of the most promising biomarkers and therapeutic targets for cancer (Hu et al, 2019), cardiovascular disease (Song et al, 2021), diabetes (Lei, Bai, et al, 2021), and other diseases (Zhang et al, 2020). However, the role of m 6 A and its underlying mechanism in PD remain largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

METTL14 is decreased and regulates m⁶A modification of α‐synuclein in Parkinson's disease

Zhang

Liao

et al. 2023

Journal of Neurochemistry

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N6-methyladenosine (m6A), an emerging modification of messenger RNA, has been implicated in many biological processes. However, its role in Parkinson's disease (PD) remains largely unknown. Here, we investigated the role of m6A modification and its underlying mechanism in PD. First, 86 individuals with PD and 86 healthy controls were recruited from a pilot multicenter cohort. Levels of m6A and its modulators in peripheral blood mononuclear cells of patients with PD and controls were measured using an m6A RNA methylation quantification kit and quantitative real-time PCR. The underlying mechanism of m6A modification in PD was investigated in vitro through RNA immunoprecipitation assay, RNA stability assay, gene silencing or overexpression, western blot, and confocal immunoassay. The results show that mRNA levels of m6A, METTL3, METTL14, and YTHDF2 in patients with PD were significantly lower than in healthy controls, and METTL14 was the main factor involved in abnormal m6A modification. Area under the curve (AUC) analysis suggests METTL14 may provide excellent diagnostic capability for PD, especially when combined with plasma α-synuclein (α-syn). Spearman correlation analysis identified that METTL14 was moderately negatively correlated with plasma α-syn and the motor function of PD.Mechanistic experiments demonstrated that Mettl14 targets and regulates the expression of the α-syn gene using its methylation function. Overexpression of Mettl14 dramatically increased m 6 A modification of α-syn mRNA and weakened its stability.Further results suggest that α-syn mRNA was modified by Mettl14 binding of an m 6 A motif in the coding region of α-syn mRNA, while the reading protein Ythdf2 was involved in recognizing m 6 A-modified α-syn mRNA. Taken together, our results reveal the potential of METTL14 as a novel diagnostic biomarker for PD and identify modification of pathogenic α-syn protein by METTL14 via an m 6 A-YTHDF2-dependent mechanism.

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Role of N6-Methyladenosine RNA Modification in Cardiovascular Disease

Cited by 4 publications

References 129 publications

Role of m6A Methylation in the Occurrence and Development of Heart Failure

Role of m6A Methylation in the Occurrence and Development of Heart Failure

The effects of RNA methylation on immune cells development and function

METTL14 is decreased and regulates m⁶A modification of α‐synuclein in Parkinson's disease

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Role of N6-Methyladenosine RNA Modification in Cardiovascular Disease

Cited by 4 publications

References 129 publications

Role of m6A Methylation in the Occurrence and Development of Heart Failure

Role of m6A Methylation in the Occurrence and Development of Heart Failure

The effects of RNA methylation on immune cells development and function

METTL14 is decreased and regulates m6A modification of α‐synuclein in Parkinson's disease

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METTL14 is decreased and regulates m⁶A modification of α‐synuclein in Parkinson's disease