Name	Cardiomyopathy
ICD	ICD-11: BC43

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	Regulator Info
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	Regulator Info
In-vitro Model	Neonatal rat ventricular cardiomyocytes (Primary myocyte cells)

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	Regulator Info
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.

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.
Ref 4	Safety and Immunogenicity of LY3415244, a Bispecific Antibody Against TIM-3 and PD-L1, in Patients With Advanced Solid Tumors. Clin Cancer Res. 2021 May 15;27(10):2773-2781. doi: 10.1158/1078-0432.CCR-20-3716. Epub 2021 Jan 13.
Ref 5	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 6	Colchicine down-regulates cytochrome P450 2B6, 2C8, 2C9, and 3A4 in human hepatocytes by affecting their glucocorticoid receptor-mediated regulation. Mol Pharmacol. 2003 Jul;64(1):160-9. doi: 10.1124/mol.64.1.160.
Ref 7	NMS-P293, a PARP-1 selective inhibitor with no trapping activity and high CNS penetration, possesses potent in vivo efficacy and represents a novel therapeutic option for brain localized metastases and glioblastoma. Cancer Res 2018;78(13 Suppl):Abstract nr 4843.