Emerging role of m<sup>6</sup>A modification in cardiovascular diseases

Peng, Liming; Long, Tianyi; Feili,; Xie, Qiying

doi:10.1002/cbin.11773

Cited by 11 publications

(10 citation statements)

References 89 publications

(140 reference statements)

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“…AAA is a degenerative disease that may lead to aortic rupture (2,5). m6A modification is the most ubiquitous mRNA modification in eukaryotes, and the role of m6A modification has been well defined in mRNA (18,21,23). Reversible m6A modification regulates a series of biological progressions, such as RNA stability, alternative splicing, and mRNA translation (19).…”

Section: Discussionmentioning

confidence: 99%

“…Reversible m6A modification regulates a series of biological progressions, such as RNA stability, alternative splicing, and mRNA translation (19). Abnormal expression of m6A modified protein or m6A binding protein or abnormal m6A modified level can lead to abnormal metabolism of m6A- modified related RNA and affect gene expression, which is closely related to the occurrence and development of many diseases (18,19,23,24). He et al reported a significantly high m6A level in AAA tissues compared to normal aortic tissues, and high m6A levels are correlated with a greater risk of AAA rupture (25).…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that epigenetic regulation of gene expression directs and maintains cellular phenotypes (16,17). N6-methyladenosine (m6A) is the most abundant and reversible internal epigenetic modification in eukaryotic organisms (18,19). In the past few years, m6A modification of messenger RNA (mRNA) or non-coding RNA has been reported to play a vital role in almost all major normal biological processes, including the selfrenewal and differentiation of embryonic stem cells, tissue development, response to heat shock or DNA damage, biological clock regulation, spermatogenesis, and transition between maternal and zygote (20,21).…”

Section: Introductionmentioning

confidence: 99%

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Bioinformatic analyses of the role of m6A RNA methylation regulators in abdominal aortic aneurysm

Fu¹,

Feng²,

Zhang³

et al. 2022

Ann Transl Med

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Background: N6-methyladenosine (m6A) is found in almost all nuclear RNAs of eukaryotes, playing an important and diverse role in many biological processes. Nonetheless, the roles of m6A regulators in abdominal aortic aneurysm (AAA) unknown. Therefore, there is a pressing need to identify m6A RNA methylation regulators in the diagnosis of AAA, determination of individualized risk, discovery of therapeutic targets, and improve understanding of pathogenesis.Methods: The GSE98278 dataset were obtained from the Gene Expression Omnibus (GEO) database to perform differential analysis of m6A-related regulators between elective stable abdominal aortic aneurysms (eAAA) and abdominal aortic aneurysm ruptured (rAAA). The random forest model was used to screen candidate m6A regulators to predict the risk of rAAA. The single sample gene set enrichment analysis (ssGSEA) method was then used to evaluate the abundance of 23 immune cells in AAA. The m6A RNA Methylation Quantification Kit was used to measure the total m6A levels of AAA and normal abdominal aorta. The terminal deoxynucleotidyl transferase mediated dUTP Nick-End Labeling (TUNEL) apoptosis assay kit was used to detect the human aortic smooth muscle cells (HASMCs) apoptotic after RBM15 knockdown. Mechanically, RBM15 knockdown was found to reduce the expression of CASP3 in an m6A-dependent manner by Western blotting, RNA immunoprecipitation (RIP), and methylated RNA immunoprecipitation-quantitative polymerase chain reaction (MeRIP-RT-PCR).Results: RBM15, WTAP, ALKBH5, and IGFBP3 were highly expressed in rAAA. In contrast, RBM15B showed opposite results (P<0.05). The high m6A level in the rAAA compared with eAAA and normal abdominal aorta (P<0.05). The random forest model was used to screen 5 candidate m6A regulators to predict the risk of rAAA. Expression of the 5 m6A methylation regulators was validated in AAA samples (P<0.05). RBM15 knockdown inhibited the apoptosis of HASMCs. RBM15 knockdown reduced the expression of CASP3 in an m6A-dependent manner. A strong correlation between the five m6A methylation regulators and immune cell infiltration was identified.Conclusions: In summary, m6A regulators play nonnegligible roles in the occurrence of rAAA. Our investigation of m6A patterns may be able to guide future immunotherapy strategies for AAA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bioinformatic analyses of the role of m6A RNA methylation regulators in abdominal aortic aneurysm

Fu¹,

Feng²,

Zhang³

et al. 2022

Ann Transl Med

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“…The m 6 A could be installed by m 6 A methyltransferase complex, containing methyltransferase-like 3 (METTL3), METTL14 and Wilms tumor 1-associated protein (WTAP). Besides, m 6 A was removed by fat mass and obesity-associated protein (FTO) and alkB homologue 5 (ALKBH5) [ 22 , 23 ]. In CRC, researchers found that the m 6 A modification level increases and METTL3 level was substantially elevated in CRC tissues.…”

Section: Discussionmentioning

confidence: 99%

N⁶-methyladenosine methyltransferase KIAA1429 elevates colorectal cancer aerobic glycolysis via HK2-dependent manner

Liu

Wang

et al. 2022

Bioengineered

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Emerging evidence has emphasized the critical roles played by N 6 -methyladenosine RNA (m 6 A) modification in colorectal carcinoma (CRC) initiation and progression. However, the roles and mechanism of m 6 A and KIAA1429 in CRC progression require further clarification. Here, our research aimed to investigate the functions of KIAA1429 in CRC tumorigenesis. Results indicated that KIAA1429 up-regulation closely correlated to the poor prognosis of CRC patients. Bio-functional assays demonstrated that KIAA1429 promoted the aerobic glycolysis, including glucose uptake, lactate production, ATP generation and extracellular acidification rate (ECAR). Mechanistically, KIAA1429 positively up-regulated HK2 level via increasing its mRNA stability by binding the m 6 A site of HK2 mRNA via m 6 A-independent manner. Collectively, our work indicates that KIAA1429 has the potential to promote CRC carcinogenesis by targeting HK2 via m 6 A-independent manner, providing insight into the critical roles of m 6 A in CRC.

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“…N6-methyladenosine (m6A) is the most prevalent type of internal RNA posttranscriptional modification in eukaryotic cells, and can occur in multiple types of RNA, including messenger RNA (mRNAs), ribosomal RNA (rRNAs), transfer RNA (tRNAs), long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) (3,(5)(6)(7). This modification is a reversible process (8) that is controlled by three main components: adenosine methyltransferases (writers), m6A-binding proteins (readers), and m6A demethylating enzymes (erasers) (9,10). The "writers" are m6A methyltransferases that catalyse the formation of the m6A modification (5), while the "erasers" are m6A demethylases that regulate the demethylation of the m6A modification (11,12).…”

Section: Introductionmentioning

confidence: 99%

m6A regulator-mediated RNA methylation modification patterns are involved in immune microenvironment regulation of coronary heart disease

Song

Wang

et al. 2022

Front. Cardiovasc. Med.

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BackgroundAlthough the roles of m6A modification in the immune responses to human diseases have been increasingly revealed, their roles in immune microenvironment regulation in coronary heart disease (CHD) are poorly understood.MethodsThe GSE20680 and GSE20681 datasets related to CHD were acquired from the Gene Expression Omnibus (GEO) database. A total of 30 m6A regulators were used to perform LASSO regression to identify the significant genes involved in CHD. Unsupervised clustering analysis was conducted using the m6A regulators to distinguish the m6A RNA methylation patterns in patients with CHD. The differentially expressed genes (DEGs) and biological characteristics, including GO and KEGG enrichment results, were assessed for the different m6A patterns to analyse the impacts of m6A regulators on CHD. Hub genes were identified, and subsequent microRNAs-mRNAs (miRNAs–mRNAs) and mRNAs-transcriptional factors (mRNA-TFs) interaction networks were constructed by the protein and protein interaction (PPI) network method using Cytoscape software. The infiltrating proportion of immune cells was assessed by ssGSEA and the CIBERSORT algorithm. Quantitative real-time PCR (qRT-PCR) was performed to detect the expression of the significant m6A regulators and hub genes.ResultsFour of 30 m6A regulators (HNRNPC, YTHDC2, YTHDF3, and ZC3H13) were identified to be significant in the development of CHD. Two m6A RNA methylation clusters were distinguished by unsupervised clustering analysis based on the expression of the 30 m6A regulators. A total of 491 genes were identified as DEGs between the two clusters. A PPI network including 308 mRNAs corresponding to proteins was constructed, and 30 genes were identified as hub genes that were enriched in the bioprocesses of peptide cross-linking, keratinocyte differentiation. Twenty-seven hub genes were found to be related to miRNAs, and seven hub genes were found to be related to TFs. Moreover, among the 30 hub genes, eight genes were found to be upregulated in CHD, and three were found to be downregulated in CHD compared to the normal people. The high m6A modification pattern was associated with a higher infiltrated abundance of immune cells.ConclusionOur findings demonstrated that m6A modification plays crucial roles in the diversity and complexity of the immune microenvironment in CHD.

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Emerging role of m⁶A modification in cardiovascular diseases

Cited by 11 publications

References 89 publications

Bioinformatic analyses of the role of m6A RNA methylation regulators in abdominal aortic aneurysm

Bioinformatic analyses of the role of m6A RNA methylation regulators in abdominal aortic aneurysm

N⁶-methyladenosine methyltransferase KIAA1429 elevates colorectal cancer aerobic glycolysis via HK2-dependent manner

m6A regulator-mediated RNA methylation modification patterns are involved in immune microenvironment regulation of coronary heart disease

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Emerging role of m6A modification in cardiovascular diseases

Cited by 11 publications

References 89 publications

Bioinformatic analyses of the role of m6A RNA methylation regulators in abdominal aortic aneurysm

Bioinformatic analyses of the role of m6A RNA methylation regulators in abdominal aortic aneurysm

N6-methyladenosine methyltransferase KIAA1429 elevates colorectal cancer aerobic glycolysis via HK2-dependent manner

m6A regulator-mediated RNA methylation modification patterns are involved in immune microenvironment regulation of coronary heart disease

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Emerging role of m⁶A modification in cardiovascular diseases

N⁶-methyladenosine methyltransferase KIAA1429 elevates colorectal cancer aerobic glycolysis via HK2-dependent manner