Examination of the associations between m6A-associated single-nucleotide polymorphisms and blood pressure

Mo, Xing‐Bo; Lei, Shu‐Feng; Zhang, Yonghong; Zhang, Huan

doi:10.1038/s41440-019-0277-8

Cited by 48 publications

(38 citation statements)

References 33 publications

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“…Zheng et al ( 118 ) reported a comprehensive database (m 6 Avar), which is a useful tool for the investigation of the association between m 6 A-related variants and disease. A previous study first made efforts to investigate the association between m 6 A-SNPs and BP by excavating data from a large-scale GWAS, and demonstrated that m 6 A-SNP may play a pivotal role in BP regulation ( 124 ). Some identified BP-related SNPs in genes have been found to be associated with coronary artery disease (CAD) ( 125 ).…”

Section: M 6 a And Cardiovascular Diseasementioning

confidence: 99%

Role of m6A RNA methylation in cardiovascular disease (Review)

et al. 2020

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N 6 -methyladenosine (m 6 A) is the most prevalent and abundant type of internal post-transcriptional RNA modification in eukaryotic cells. Multiple types of RNA, including mRNAs, rRNAs, tRNAs, long non-coding RNAs and microRNAs, are involved in m 6 A methylation. The biological function of m 6 A modification is dynamically and reversibly mediated by methyltransferases (writers), demethylases (erasers) and m 6 A binding proteins (readers). The methyltransferase complex is responsible for the catalyzation of m 6 A modification and is typically made up of methyltransferase-like (METTL)3, METTL14 and Wilms tumor 1-associated protein. Erasers remove methylation by fat mass and obesity-associated protein and ALKB homolog 5. Readers play a role through the recognition of m 6 A-modified targeted RNA. The YT521-B homology domain family, heterogeneous nuclear ribonucleoprotein and insulin-like growth factor 2 mRNA-binding protein serve as m 6 A readers. The m 6 A methylation on transcripts plays a pivotal role in the regulation of downstream molecular events and biological functions, such as RNA splicing, transport, stability and translatability at the post-transcriptional level. The dysregulation of m 6 A modification is associated with cancer, drug resistance, virus replication and the pluripotency of embryonic stem cells. Recently, a number of studies have identified aberrant m 6 A methylation in cardiovascular diseases (CVDs), including cardiac hypertrophy, heart failure, arterial aneurysm, vascular calcification and pulmonary hypertension. The aim of the present review article was to summarize the recent research progress on the role of m 6 A modification in CVD and give a brief perspective on its prospective applications in CVD.

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Section: M 6 a And Cardiovascular Diseasementioning

confidence: 99%

Role of m6A RNA methylation in cardiovascular disease (Review)

et al. 2020

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“…Suppressing adipogenesis by promoting cell cycle transition in mitotic clonal expansion [89] YTHDF2 Inhibiting autophagy and adipogenesis by decreasing protein expression of ATG5 and ATG7 and shortening the lifespan of their m 6 A-modified mRNAs [87] Suppressing adipogenesis by increasing m 6 A methylation of CCNA2 and CDK2 and reversing the methylation effect of FTO on CCNA2 and CDK2 [90,91] Inhibiting adipogenesis via the downregulation of CCND1 [92] NAFLD FTO Down-regulating mitochondrial content and up-regulating TG deposition [101] Promoting hepatic fat accumulation by increasing the expression of lipogenic genes, including FASN, SCD and MOGAT1, and intracellular TG level in HepG2 cells [101] Increasing oxidative stress and lipid deposition [99] YTHDF2 Increasing lipid accumulation by decreasing both PPARα mRNA lifetime and expression [105] METTL3 Increasing lipid accumulation by decreasing both PPARα mRNA lifetime and expression [105] Hypertension m 6 A-SNPs EncodIing β1-adrenoreceptor, a hypertension-susceptibility candidate gene [108,109] Altering BP-related gene expression, mRNA stability and homeostasis [110] Cardiovascular diseases FTO Decreasing fibrosis and enhancing angiogenesis in mouse models of myocardial infarction [111] METTL3 Driving cardiomyocyte hypertrophy by catalyzing methylation of m 6 A on certain subsets of mRNAs [112] Decreasing eccentric cardiomyocyte remodeling and dysfunction [112] Inhibiting cellular autophagic flux and promoting apoptosis in hypoxia/reoxygenation-treated cardiomyocytes [113] Osteoporosis METTL3 Inhibiting adipogenesis and adipogenic differentiation via JAK1/STAT5/C/EBPβ pathway in bone marrow stem cells [119] Inhibiting osteoporosis pathological phenotypes, consisting of decreased bone mass and increased marrow adiposity via PTH/PTH1R signaling axis [118] FTO Promoting the differentiation of adipocyte and osteoblast by upregulating GDF11-FTO-PPARγ signalling way [116] Enhancing the stability of mRNA of proteins which function to protect osteoblasts from genotoxic damage through Hspa1a-NF-κB signaling way [120] Immune-related MDs ALKBH5 Expressing highly in organs enriched in immune cells with frequent immune reactions [10,123] METTL3 Stimulating T cell activation and the development of T lymphocytes in the thymus by regulating the translation of CD40, CD80 and TLR4 signaling adaptor TIRAP transcripts in den...…”

Section: Mettl14mentioning

confidence: 99%

“…In addition, the m 6 A-SNPs (Arg389Gly, rs1801253; Ser49Gly, rs1801253) can develop hypertension as they can encode β1-adrenoreceptor, a hypertension-susceptibility candidate gene [108,109]. rs9847953 and rs197922 have regulatory potentials to alter BP related gene expression, mRNA stability and homeostasis [110]. The m 6 A RNA modifications also involve in various mechanisms of cardiovascular diseases.…”

Section: A Methylation In Hypertension and Cardiovascular Diseasesmentioning

confidence: 99%

RNA N6-methyladenosine: a promising molecular target in metabolic diseases

Wang

Huang

et al. 2020

Cell Biosci

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N6-methyladenosine is a prevalent and abundant transcriptome modification, and its methylation regulates the various aspects of RNAs, including transcription, translation, processing and metabolism. The methylation of N6-methyladenosine is highly associated with numerous cellular processes, which plays important roles in the development of physiological process and diseases. The high prevalence of metabolic diseases poses a serious threat to human health, but its pathological mechanisms remain poorly understood. Recent studies have reported that the progression of metabolic diseases is closely related to the expression of RNA N6-methyladenosine modification. In this review, we aim to summarize the biological and clinical significance of RNA N6-methyladenosine modification in metabolic diseases, including obesity, type 2 diabetes, non-alcoholic fatty liver disease, hypertension, cardiovascular diseases, osteoporosis and immune-related metabolic diseases.

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“…N6-methyladenosine (m6A) is an epigenetic RNA modification that occurs in most eukaryotes. Recent studies have identified multiple proteins that are associated with m6A in the regulation of blood pressure (6), cardiac gene expression and cell growth (7), cell survival, and intracellular signaling (8). Previous studies have demonstrated the functional importance of cardiac Fat mass and obesity-associated protein (FTO)dependent m6A methylome during myocardial infarction (9) and cardiac growth control by Methyltransferase Like 3 (METTL3) (10).…”

Section: Introductionmentioning

confidence: 99%

Transcriptome and N6-Methyladenosine RNA Methylome Analyses in Aortic Dissection and Normal Human Aorta

Zhou

Chen

Zhou

et al. 2021

Front. Cardiovasc. Med.

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Objective: To investigate the N6-methyladenosine (m6A) modification and the expressions of the m6A regulatory genes in the acute aortic dissection (AD).Methods: MeRIP-seq and RNA-seq experiments of aortic media tissue samples obtained from AD (n = 4) and Controls (n = 4) were conducted. m6A methylation quantification was used to measure the total mRNA m6A level. The five m6A regulators mRNA expressions were analyzed by quantitative polymerase chain reaction (qPCR). Western blot analyses and immunofluorescence staining were used to detect the difference of METTL14 protein expression in the aortas of AD and Normal.Results: Among AD patients, we detected significantly elevated levels of m6A in total RNA. Compared with the normal group, the up methylated coding genes of AD were primarily enriched in the processes associated with extracellular fibril organization, while the genes with down methylation were enriched in the processes associated with cell death regulation. Furthermore, many differentially methylated m6A sites (DMMSs) coding proteins were mainly annotated during the extracellular matrix and inflammatory responses.Conclusions: These findings indicate that differential m6A methylation and m6A regulatory genes, including MTEEL14 and FTO, may act on functional genes through RNA modification, thereby regulating the pathogenesis of aortic dissection.

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Examination of the associations between m6A-associated single-nucleotide polymorphisms and blood pressure

Cited by 48 publications

References 33 publications

Role of m6A RNA methylation in cardiovascular disease (Review)

Role of m6A RNA methylation in cardiovascular disease (Review)

RNA N6-methyladenosine: a promising molecular target in metabolic diseases

Transcriptome and N6-Methyladenosine RNA Methylome Analyses in Aortic Dissection and Normal Human Aorta

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