General Information of the Disease (ID: M6ADIS0100)
Name
Cardiomegaly
ICD
ICD-11: BC45
Full List of Target Gene(s) of This m6A-centered Disease Response
microRNA 221 (MIR221)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary METTL3 positively modulates the pri-miR-221/222 maturation process in an m6A-dependent manner and subsequently activates Wnt/Beta-catenin signaling by inhibiting DKK2, thus promoting Ang-II-induced cardiac hypertrophy.
Responsed Disease Cardiomegaly [ICD-11: BC45]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response Wnt signaling pathway hsa04310
In-vitro Model NRCMs (Primary neonatal rat cardiomyocytes (NRCMs)NRCMs were prepared from the hearts of 2- to 3-day-old SD rats according to the following protocol)
In-vivo Model The pump was prefilled with Ang-II or saline and then incubated in sterile saline at 37 ℃ for 48 h. After the mice were anesthetized with 3.0% isoflurane mixed with oxygen, an incision was made on the back skin of the mice, and the pump was implanted into the subcutaneous area, followed by suturing the incision. After the operation, the mice were given buprenorphine (0.1 mg/kg) to reach analgesia. Finally, the regaining consciousness mice were returned to cages and fed until the end of the experiment.
microRNA 222 (MIR222)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary METTL3 positively modulates the pri-miR221/pri-miR-222 maturation process in an m6A-dependent manner and subsequently activates Wnt/Beta-catenin signaling by inhibiting DKK2, thus promoting Ang-II-induced cardiac hypertrophy.
Responsed Disease Cardiomegaly [ICD-11: BC45]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response Wnt signaling pathway hsa04310
In-vitro Model NRCMs (Primary neonatal rat cardiomyocytes (NRCMs)NRCMs were prepared from the hearts of 2- to 3-day-old SD rats according to the following protocol)
In-vivo Model The pump was prefilled with Ang-II or saline and then incubated in sterile saline at 37 ℃ for 48 h. After the mice were anesthetized with 3.0% isoflurane mixed with oxygen, an incision was made on the back skin of the mice, and the pump was implanted into the subcutaneous area, followed by suturing the incision. After the operation, the mice were given buprenorphine (0.1 mg/kg) to reach analgesia. Finally, the regaining consciousness mice were returned to cages and fed until the end of the experiment.
hsa-miR-133a-3p
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [2]
Response Summary IGF2BP2 physically interacted with AGO2 and increased more hsa-miR-133a-3p accumulation on its target site.m6A modification promoted the repression of specific miRNA during heart development and hypertrophy.
Responsed Disease Cardiomegaly [ICD-11: BC45]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) READER
Target Regulation Up regulation
In-vitro Model CM Pancreatic insulinoma Homo sapiens CVCL_H246
In-vivo Model Neonatal mouse cardiomyocytes (CMs) were blinded to isolate from 7-10 cases of postnatal 1-day old wildtype C57/B mice and cultured using Pierce Primary Cardi Page 10.omyocyte Isolation Kit (Thermo Fisher Scientific) as the manufacturer's instructions.
Full List of Crosstalk(s) between m6A Modification and Epigenetic Regulation Related to This Disease
In total 5 item(s) under this disease
Crosstalk ID: M6ACROT02042
m6A Regulator Methyltransferase-like 3 (METTL3)
m6A Target Protein mono-ADP-ribosyltransferase PARP10 (PARP10)
Epigenetic Regulator DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target Methyltransferase-like protein 3 (METTL3)
Crosstalk relationship DNA modification → m6A
Drug Ang II
Crosstalk ID: M6ACROT05086
m6A Regulator Methyltransferase-like 3 (METTL3)
m6A Target Protein mono-ADP-ribosyltransferase PARP10 (PARP10)
Epigenetic Regulator Cardiac-hypertrophy-associated piRNA
Regulated Target Methyltransferase-like protein 3 (METTL3)
Crosstalk relationship ncRNA → m6A
Crosstalk ID: M6ACROT05495
m6A Regulator Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)
m6A Target miR-133a
Epigenetic Regulator hsa-miR-133a-3p
Regulated Target Protein argonaute-2 (AGO2)
Crosstalk relationship m6A → ncRNA
Crosstalk ID: M6ACROT05561
m6A Regulator Methyltransferase-like 3 (METTL3)
m6A Target microRNA 221 (MIR221)
Epigenetic Regulator MicroRNA 221 (MIR221)
Regulated Target Dickkopf-related protein 2 (DKK2)
Crosstalk relationship m6A → ncRNA
Crosstalk ID: M6ACROT05562
m6A Regulator Methyltransferase-like 3 (METTL3)
m6A Target microRNA 222 (MIR222)
Epigenetic Regulator MicroRNA 222 (MIR222)
Regulated Target Dickkopf-related protein 2 (DKK2)
Crosstalk relationship m6A → ncRNA
References
Ref 1 METTL3 mediates Ang-II-induced cardiac hypertrophy through accelerating pri-miR-221/222 maturation in an m6A-dependent manner. Cell Mol Biol Lett. 2022 Jul 14;27(1):55. doi: 10.1186/s11658-022-00349-1.
Ref 2 m6A modification promotes miR-133a repression during cardiac development and hypertrophy via IGF2BP2. Cell Death Discov. 2021 Jun 26;7(1):157. doi: 10.1038/s41420-021-00552-7.
Ref 3 ClinicalTrials.gov (NCT02575261) CAR-T Cell Immunotherapy for EphA2 Positive Malignant Glioma Patients