General Information of the Disease (ID: M6ADIS0015)
Name
Retinopathy
ICD
ICD-11: 9B71
Full List of Target Gene(s) of This m6A-centered Disease Response
Integrin beta-1 (ITGB1)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [3]
Response Summary KAT1 triggers YTHDF2-mediated Integrin beta-1 (ITGB1) mRNA instability to alleviate the progression of DR.
Responsed Disease Diabetic retinopathy [ICD-11: 9B71.0]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
Target Regulation Down regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process RNA stability
In-vitro Model RMECs (Retinal microvascular endothelial cells (RMECs) purchased from Olaf (Worcester, MA, USA))
rMCs (Retinal Muller cells (rMCs) from Kerafast Inc. (Boston, MA))
In-vivo Model Male mice (8-10 weeks old, SLAC Laboratory Animal Co., Ltd., Shanghai, China) were administrated with STZ through intraperitoneal injection (I.P) for continuous 5 days (d).
TNF alpha-induced protein 3 (TNFAIP3)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [4]
Response Summary Lower expression TNF alpha-induced protein 3 (TNFAIP3) resulted in the enhanced M1 polarization of retinal microglia in diabetic retinopathy, which was caused by ALKBH5 mediated m6A modification.
Responsed Disease Diabetic retinopathy [ICD-11: 9B71.0]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
Target Regulation Down regulation
In-vitro Model BV-2 Normal Mus musculus CVCL_0182
In-vivo Model The male Sprague-Dawley rats (8 weeks old, 200-220 g) were purchased from the Laboratory Animal Center of Sun Yat-sen University. Streptozotocin (Sigma, USA) was given by intraperitoneal injection at a dose of 60 mg/Kg to induce diabetics rats, while the control rats were given by empty citrate buffer. One week after induction, those rats with blood glucose levels > 16.7 mmol/L for three times were considered as successful inducted diabetes. All the rats did not receive insulin during the experiments.In the intraocular injection experiments, rats confirmed as the DM model (blood glucose levels > 16.7 mmol/L for three times) were anesthetized with an intraperitoneal injection of sodium pentobarbital (50 mg/Kg). A total of 10 ul DMEM with 1*109 TU lentiviruses (A20-overexpression, OE-A20 group) or the same volume of DMEM with control lentiviruses (OE-NC group) was injected into the vitreous cavity using a 33-gauge needle. This treatment was performed one time per month, and the rats were sacrificed for further experiments at the 3 months.
hsa-miR-25-3p
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [7]
Response Summary METTL3 involves in the pathogenesis of diabetic retinopathy (DR). Both METTL3 mRNA and hsa-miR-25-3p were low-expressed in the peripheral venous blood samples of diabetes mellitus (DM) patients compared to normal volunteers, and high-glucose inhibited METTL3 and miR-25-3p expressions in RPE cells. Overexpression of METTL3 attenuates high-glucose induced RPE cell pyroptosis by regulating miR-25-3p/PTEN/Akt signaling cascade through DGCR8.
Responsed Disease Diabetic retinopathy [ICD-11: 9B71.0]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Cell viability
Cell apoptosis
In-vitro Model ARPE-19 Normal Homo sapiens CVCL_0145
Full List of Crosstalk(s) between m6A Modification and Epigenetic Regulation Related to This Disease
In total 7 item(s) under this disease
Crosstalk ID: M6ACROT03086
m6A Regulator Fat mass and obesity-associated protein (FTO)
m6A Target Cyclin-dependent kinase 2 (CDK2)
Epigenetic Regulator Histone acetyltransferase p300 (P300)
Regulated Target Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship Histone modification → m6A
Drug FB23-2
Crosstalk ID: M6ACROT03087
m6A Regulator YTH domain-containing family protein 2 (YTHDF2)
m6A Target Cyclin-dependent kinase 2 (CDK2)
Epigenetic Regulator Histone acetyltransferase p300 (P300)
Regulated Target Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship Histone modification → m6A
Drug FB23-2
Crosstalk ID: M6ACROT03215
m6A Regulator YTH domain-containing family protein 2 (YTHDF2)
m6A Target Integrin beta-1 (ITGB1)
Epigenetic Regulator Histone acetyltransferase type B catalytic subunit (HAT1)
Regulated Target Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship Histone modification → m6A
Crosstalk ID: M6ACROT05118
m6A Regulator Far upstream element-binding protein 2 (KHSRP)
m6A Target Myocardin-related transcription factor A (MKL1)
Epigenetic Regulator Small nucleolar RNA host gene (SNHG7)
Regulated Target KH-type splicing regulatory protein (KHSRP)
Crosstalk relationship ncRNA → m6A
Crosstalk ID: M6ACROT05432
m6A Regulator Methyltransferase-like 3 (METTL3)
m6A Target hsa-miR-25-3p
Epigenetic Regulator hsa-miR-25-3p
Regulated Target Mutated in multiple advanced cancers 1 (PTEN)
Crosstalk relationship m6A → ncRNA
Crosstalk ID: M6ACROT05768
m6A Regulator Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)
m6A Target HOXD antisense growth-associated long non-coding RNA (HAGLR)
Epigenetic Regulator HOXD antisense growth-associated long non-coding RNA (HAGLR)
Regulated Target hsa-miR-106b-5p
Crosstalk relationship m6A → ncRNA
Crosstalk ID: M6ACROT05895
m6A Regulator Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)
m6A Target HOXD antisense growth-associated long non-coding RNA (HAGLR)
Epigenetic Regulator hsa-miR-106b-5p
Regulated Target Mutated in multiple advanced cancers 1 (PTEN)
Crosstalk relationship m6A → ncRNA
References
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Ref 3 KAT1 triggers YTHDF2-mediated ITGB1 mRNA instability to alleviate the progression of diabetic retinopathy. Pharmacol Res. 2021 Aug;170:105713. doi: 10.1016/j.phrs.2021.105713. Epub 2021 Jun 5.
Ref 4 ALKBH5-Mediated m(6)A Modification of A20 Regulates Microglia Polarization in Diabetic Retinopathy. Front Immunol. 2022 Mar 1;13:813979. doi: 10.3389/fimmu.2022.813979. eCollection 2022.
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Ref 7 Overexpression of METTL3 attenuates high-glucose induced RPE cell pyroptosis by regulating miR-25-3p/PTEN/Akt signaling cascade through DGCR8. Aging (Albany NY). 2020 May 4;12(9):8137-8150. doi: 10.18632/aging.103130. Epub 2020 May 4.
Ref 8 Discovery and Biological Profiling of Potent and Selective mTOR Inhibitor GDC-0349. ACS Med Chem Lett. 2012 Nov 29;4(1):103-7. doi: 10.1021/ml3003132. eCollection 2013 Jan 10.