m6A Modification—Association with Oxidative Stress and Implications on Eye Diseases
Abstract
:1. Introduction
2. m6A Modification
2.1. Writers
2.2. Erasers
2.3. Readers
3. m6A Modification and Oxidative Stress-Related Eye Diseases
3.1. Corneal Disease
3.2. Cataract
3.3. Glaucoma
3.4. Uveitis
3.5. Retinopathy
3.5.1. Diabetic Retinopathy (DR)
3.5.2. Retinopathy of Prematurity (ROP)
3.5.3. Retinitis Pigmentosa (RP)
3.5.4. Age-Related Macular Degeneration (AMD)
3.6. Traumatic Optic Neuropathy (TON)
3.7. Ocular Tumor
Eye Diseases | Total m6A Level | Enzymes | Functions |
---|---|---|---|
Corneal Neovascularization | N/A | METTL3 | Targets stem cell regulatory factors Ahnak and Ddit4 to regulate limbal stem cell proliferation and migration [41]. |
Down | FTO | Increases the expression of FAK to promote vascular endothelial cell function and angiogenesis [39]. | |
Cataract | Up | METTL3 | Regulates the lens epithelial cells proliferation and apoptosis by targeting the 3’UTR of ICAM-1 to stabilize mRNA stability [54]. |
Glaucoma | N/A | YTHDF2 | Targets Hspa12a and Islr2 to affect the tolerance of RGC to acute intraocular hypertension [67]. |
Uveitis | Down | YTHDF1 | Increases Sirt1 expression thus restraining M1 polarization and migration in microglia [74]. |
N/A | FTO | Promotes ATF4 expression via both m6A-dependent manner and PERK pathway, thereby reducing the inflammatory response [75]. | |
Diabetic Retinopathy | N/A | METTL3 | Targets miR-25-3p/PTEN/AKT signaling cascade to enhance RPE cell viability [93]. |
Up | METTL3 | Reduces PKC-η, FAT4 and PDGFRA mRNA expression thus aggravating pericyte dysfunction [90]. | |
N/A | FTO | Promotes the mRNA stability of NLRP3 to activate pyroptosis in RPE cells [94]. | |
N/A | ALKBH5 | Protects A20 mRNA from degradation to reduce M1 microglia polarization [92]. | |
N/A | YTHDF2 | Promotes the instability of IGTB1 mRNA which is a positive regulator of the FAK/PI3K/AKT signaling pathway [91]. | |
Retinopathy of Prematurity | Up | METTL3 | Regulates Wnt signaling activation by targeting LRP6 and DVL1 [40]. |
Retinitis Pigmentosa | Down | METTL14 | Inhibits expression of MAP2 which interacts with NEUROD1 to induce pathologic changes in RPE cells [104]. |
Age-related Macular Degeneration | N/A | FTO | Rescues RPE from degeneration by inhibiting PKA/CREB signaling [109]. |
Ocular Melanoma | Down | METTL3, ALKBH5 | Regulates the translation of the tumor suppressor gene HINT2 to regulate ocular melanoma tumorigenesis [117]. |
N/A | ALKBH5 | Increases FOXM1 expression to promote invasion, migration, and epithelial–mesenchymal transition in UM cells [118]. | |
Up | METTL3 | Enhances UM cell proliferation, migration, and invasion by promoting c-Met translation [119]. | |
N/A | METTL3 | Increases RNA and protein level of BACE2, which accelerates tumorigenesis via TMEM38B/Ca2+ pathway [120]. | |
N/A | YTHDF2 | Promotes degradation of PER1 and TP53 mRNA, thereby accelerating tumorigenesis of ocular melanoma [121]. | |
Retinoblastoma | N/A | METTL3 | Promotes RB progression in vivo and in vitro through PI3K/AKT/mTOR pathway [126]. |
4. Treatment
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviation
AAV | adeno-associated virus |
AGEs | advanced glycation end products |
AH | aqueous humor |
ALKBH5 | alkB homolog 5 |
AMD | age-related macular degeneration |
AML | acute myeloid leukemia |
AOPP | advanced oxidation protein product |
ARCC | age-related cortical cataract |
BACE2 | beta-secretase 2 |
CAT | catalases |
CM | conjunctival melanoma |
DDIT4 | DNA damage inducible transcript 4 |
DR | diabetic retinopathy |
DVL1 | dishevelled segment polarity protein 1 |
eIF3 | eukaryotic initiation factor 3 |
EPO | erythropoietin |
f6A | N6-formyladenosine |
FAK | focal adhesion kinase |
FAT4 | FAT atypical cadherin 4 |
FOXM1 | forkhead box M1 |
FTO | fat mass and obesity-associated protein |
GPXs | glutathione peroxidases |
GSCs | glioma stem cells |
GSH | glutathione |
GSTs | glutathione S-transferases |
HINT2 | histidine triad nucleotide binding protein 2 |
hm5C | 5-hydroxymethylcytosine |
HNRNPC | heterogeneous nuclear ribonucleoprotein C |
Hspa12a | heat shock protein family A member 12A |
HUVECs | human umbilical vein endothelial cells |
ICAM1 | intercellular adhesion molecule 1 |
IGF2BP1 | Insulin-like growth factor 2 mRNA binding protein 1 |
IOP | intraocular pressure |
Islr2 | immunoglobulin superfamily containing leucine rich repeat 2 |
ITGB1 | integrin subunit beta 1 |
KAT1 | lysine acetyltransferase 1 |
LCA10 | leber congenital amaurosis 10 |
lncRNA | long noncoding RNA |
LRP6 | LDL receptor related protein 6 |
m1A | N1-methyladenosine |
m5C | 5-methylcytosine |
m6A | N6-methyladenosine |
MAP2 | microtubule associated protein 2 |
MDA | malondialdehyde |
MEF | mouse embryonic fibroblast |
METTL3 | methyltransferase-like 3 |
miRNA | microRNA |
mRNA | messenger RNA |
mtDNA | mitochondrial DNA |
NEUROD1 | neuronal differentiation 1 |
NPs | nanoparticles |
NSCLC | non-small cell lung cancer |
OIR | oxygen-induced retinopathy |
OS | oxidative stress |
PDGFRA | platelet derived growth factor receptor alpha |
PKC | protein kinase C |
PRDXs | peroxiredoxins |
p-STAT3 | phospho-signal transducer and activator of transcription 3 |
RB | retinoblastoma |
RBM15 | RNA-binding motif protein 15 |
RGCs | retinal ganglion cells |
ROP | retinopathy of prematurity |
ROS | reactive oxygen species |
RP | retinitis pigmentosa |
RPE | retinal pigment epithelium |
rRNA | ribosomal RNA |
SAM | S-adenosylmethionine |
snoRNA | small nucleolar RNA |
snRNA | small nuclear RNA |
SODs | superoxide dismutases |
TM | trabecular meshwork |
tmRNA | transfer-messenger RNA |
TON | traumatic optic neuropathy |
tRNA | transfer RNA |
TRXPs | thioredoxin peroxidases |
TRXs | thioredoxins |
UM | uveal melanoma |
VEGF | vascular endothelial growth factor |
VIRMA | vir-like m6A methyltransferase-associated protein |
WTAP | Wilms tumor 1 associated protein |
YTHDC1 | YTH domain containing 1 |
YTHDF1 | YTH N6-methyladenosine RNA binding protein 1 |
ZC3H13 | zinc finger CCCH-type containing 13 |
2′-O-Me | ribosemethylation |
3-NP | 3-nitropropionic acid |
4-HNE | 4-hydroxy-2-nonenal |
8-OHdG | 8-OH 2-deoxyguanosine |
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Targets | Inhibitors | Diseases or Cell Lines | Functions |
---|---|---|---|
FTO | Rhein | BE(2)-C cells | Reversibly binds FTO enzyme and competitively prevents the recognition of m6A substrates [141]. |
Meclofenamic Acid | HeLa cells | Inhibits FTO demethylation of an m6A-containing ssDNA or ssRNA [142]. | |
R-2HG | human leukemia cell lines and leukemic mouse models | Inhibits leukemia cell proliferation/viability and promotes cell-cycle arrest and apoptosis [143]. | |
FB23/FB23-2 | human acute myeloid leukemia (AML) cell lines and primary blast AML cells | Suppresses proliferation and promotes the differentiation/apoptosis of human AML cell line cells and primary blast AML cells in vivo and in vitro [144]. | |
Fluorescein | HeLa cells | Inhibits FTO demethylation inside live cells [145]. | |
CS1/CS2 | AML cell lines, primary AML cells, and leukemic mouse models | Attenuates leukemia stem/initiating cell self-renewal, reprogram immune response, and immune evasion [146]. | |
Dac51 | B16-OVA, LLC, and MC38 cells, and tumor-bearing mice | Blocks FTO-mediated immune evasion [147]. | |
ALKBH5 | MV1035 | U87-MG and H460 cells | Reduces U87 glioblastoma cell line migration and invasiveness [148]. |
METTL3 | STM2457 | AML cell lines, and leukemic mouse models | Reduces AML growth and increases differentiation and apoptosis [149]. |
UZH1a/UZH1b | MOLM-13, U2OS, and HEK293T cells | Reduces the m6A/A ratio in mRNAs of AML MOLM-13 cells, osteosarcoma U2OS cells, and the embryonic kidney cell line HEK293T [150]. |
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Ni, Y.; Zhang, H.; Chu, L.; Zhao, Y. m6A Modification—Association with Oxidative Stress and Implications on Eye Diseases. Antioxidants 2023, 12, 510. https://doi.org/10.3390/antiox12020510
Ni Y, Zhang H, Chu L, Zhao Y. m6A Modification—Association with Oxidative Stress and Implications on Eye Diseases. Antioxidants. 2023; 12(2):510. https://doi.org/10.3390/antiox12020510
Chicago/Turabian StyleNi, Yueqi, Hong Zhang, Liang Chu, and Yin Zhao. 2023. "m6A Modification—Association with Oxidative Stress and Implications on Eye Diseases" Antioxidants 12, no. 2: 510. https://doi.org/10.3390/antiox12020510