General Information of the Disease (ID: M6ADIS0142)
Name
Cardiomyopathy
ICD
ICD-11: BC43
Full List of Target Gene(s) of This m6A-centered Disease Response
Forkhead box protein O3 (FOXO3)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary ALKBH5 was upregulated in the cardiomyocytes of diabetic cardiomyopathy mice and posttranscriptionally activated Forkhead box protein O3 (FOXO3) by m6A demethylation in an m6A-YTHDF2-dependent manner.This work reveals the key function of the ALKBH5-FOXO3-CDR1as/Hippo signaling pathway in DCM and provides insight into the critical roles of m6A methylation in DCM.
Responsed Disease Diabetic cardiomyopathy [ICD-11: BC43.7]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
Target Regulation Up regulation
Pathway Response Hippo signaling pathway hsa04390
FoxO signaling pathway hsa04068
Cell Process Cell apoptosis
In-vitro Model Neonatal rat ventricular cardiomyocytes (Primary myocyte cells)
In-vivo Model The model mice were intraperitoneally injected with streptozotocin (STZ; Sigma-Aldrich Corp., USA). The dose of STZ was 50 mg/kg for 5 days. 7 days after the last injection, blood glucose concentrations were recorded. Mouse models of diabetes were considered established when fasting blood glucose concentrations reached >11.1 mmol/L, and body weight was measured.
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [2]
Response Summary This study suggests that YTHDC1 plays crucial role in regulating the normal contractile function and the development of dilated cardiomyopathy.
Responsed Disease Dilated cardiomyopathy [ICD-11: BC43.0]
Target Regulator YTH domain-containing protein 1 (YTHDC1) READER
In-vitro Model Neonatal rat ventricular cardiomyocytes (Primary myocyte cells)
Ubiquitin domain-containing protein TINC (TINCR)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [3]
Response Summary METTL14 suppressed pyroptosis and diabetic cardiomyopathy via downregulating lncRNA Ubiquitin domain-containing protein TINC (TINCR), which further decreased the expression of key pyroptosis-related protein, NLRP3.
Responsed Disease Diabetic cardiomyopathy [ICD-11: BC43.7]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Down regulation
In-vitro Model neonatal ventricular myocytes (Mouse hearts were enzymatically digested to acquire the primary neonatal ventricular myocytes)
H9c2(2-1) Normal Rattus norvegicus CVCL_0286
In-vivo Model The diabetic model was constructed by a single intraperitoneal injection of streptozotocin (65 mg/kg), which imitates a model of type 1 diabetes. The fasting blood glucose was measured one week after injection. Only rats with glucose levels higher than 16.7 mmol/L were defined as diabetic. Cardiac function was investigated seven days following the last treatment, and the heart tissues were then isolated for expression analyses. The lentivirus vector used for silencing or overexpressing specific genes were dissolved in 50uL saline at the concentration of 1 × 109 TU with one dose after the animal model was established. NLRP3 inhibitor MCC950 (10 mg/kg) was intraperitoneally injected 30 min before streptozotocin treatment.
References
Ref 1 CircRNA CDR1as promotes cardiomyocyte apoptosis through activating hippo signaling pathway in diabetic cardiomyopathy. Eur J Pharmacol. 2022 May 5;922:174915. doi: 10.1016/j.ejphar.2022.174915. Epub 2022 Mar 24.
Ref 2 Depletion of m(6) A reader protein YTHDC1 induces dilated cardiomyopathy by abnormal splicing of Titin. J Cell Mol Med. 2021 Dec;25(23):10879-10891. doi: 10.1111/jcmm.16955. Epub 2021 Oct 30.
Ref 3 METTL14 suppresses pyroptosis and diabetic cardiomyopathy by downregulating TINCR lncRNA. Cell Death Dis. 2022 Jan 10;13(1):38. doi: 10.1038/s41419-021-04484-z.