Table 1.
Multiple functions exerted by m6A RNA methylation in various cardiovascular diseases
| Disease | Molecule | Target gene | Function | Regulation | Mechanism | Reference |
| Ischemic heart diseases | METTL3 | TFEB | Writer | Up-regulation | Silencing METTL3 enhances autophagic flux and inhibits apoptosis in H/R-treated cardiomyocytes by TFEB | Pastore et al., 2016 |
| ALKBH5 | TFEB | Eraser | Down-regulation | ALKBH5 overexpression enhances autophagic flux and inhibits apoptosis in H/R-treated cardiomyocytes by TFEB | Pastore et al., 2016 | |
| Heart failure (HF) | FTO | SERCA2a | Eraser | Down-regulation | FTO overexpression improves cardiomyocyte function and attenuatis cardiac remodeling in HF by regulating SERCA2a | Mathiyalagan et al., 2019 |
| Myocardial infarction (MI) | FTO | Nppa/MYH7/Ryr2/SERCA2a | Eraser | Down-regulation | FTO overexpression protects and repairs cardiomyocyte function through improving cardiac homeostasis after MI | Mathiyalagan et al., 2019 |
| Hypertrophy | METTL3 | MAP3K6/MAP4K5/MAPK14/Nppa/Nppb | Writer | Up-regulation | Silencing METTL3 maintains normal cardiac function in response to hypertrophic stimuli through stress-response mechanism | Dorn et al., 2019 |
| FTO | Eraser | Up-regulation | Silencing FTO blunts hypertrophy of NRCM in response to α-adrenergic stimulation | Kmietczyk et al., 2019 | ||
| Abnormal cardiac development | METTL3/14 | HuR | Writer | Down-regulation | The level of METTL3 expression maintains and even improves the self-renewal capability of mESCs | Wang et al., 2014 |
| FTO | Eraser | Mutation | FTO plays an important role in early development of human central nervous and cardiovascular systems | Daoud et al., 2016 | ||
| Obesity | FTO | Angptl4 | Eraser | Up-regulation | FTO influences triglyceride metabolism in adipocytes and by post-transcriptional regulation of Angptl4 | Wang et al., 2015 |
| YTHDF2 | PPARγ/C/EBPα | Reader | Down-regulation | Adipogenesis of porcine adipocytes can be led by a loss of m6A on FAM134B through m6A-YTHDF2-dependent way | Cai et al.,2019 | |
| Diabetes mellitus | FTO | FOXO1/G6PC/DGAT2 | Eraser | Up-regulation | FTO expression is highly related tothe impairment of plasma glucose and even multiple complications by altering target genes | Yang et al., 2019 |
| Abnormal circadian rhythm | METTL3 | Per2/Arntl | Writer | Down-regulation | Silencing METTL3 can elicit circadian period elongation and RNA processing delay by distributing clock genes Per2 and Arntl | Fustin et al., 2013 |
| Inflammation | METTL3 | MyD88S | Writer | Up-regulation | Silencing METTL3 attenuates theinflammatory response via regulating MyD88S in LPS-induced hDPCs | Liu et al., 2019 |
m6A: N 6-methyladenosine; METTL3: methyltransferase-like 3; ALKBH5: ALKB homolog 5; FTO: fat mass-and obesity-related protein; YTHDF2: YT521-B homology (YTH) domain family 2; TFEB: transcription factor EB; SERCA2a: sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2a; Nppa: natriuretic peptide precursor (Npp)-A; MYH7: β-myosin heavy chain 7; Ryr2: ryanodine receptor 2; MAP3K6: mitogen-activated protein kinase (MAPK) kinase kinase 6; MAP4K5: MAPK kinase kinase kinase 5; HuR: human antigen R; Angptl4: angiopoietin-like 4; PPARγ: peroxisome proliferator-activated receptor γ; C/EBPα: CCAAT enhancer-binding protein α; FOXO1: forkhead box O1; G6PC: glucose-6-phosphatase (G6Pase) catalytic subunit; DGAT2: diacylglycerol acyltransferase 2; Per2: period 2; Arntl: aryl hydrocarbon receptor nuclear translocator like; MyD88S: splice variant of myeloid differentiation factor 88; H/R: hypoxia/reoxygenation; NRCM: neonatal rat cardiac myocyte; mESCs: mouse embryonic stem cells; FAM134B: family with sequence similarity 134 member B; LPS: lipopolysaccharide; hDPCs: human dental pulp cells