m6A-centered Disease Response Information

General Information of the Disease (ID: M6ADIS0113)
Name
Ossification of spinal ligaments
ICD
ICD-11: FA83
Full List of Target Gene(s) of This m6A-centered Disease Response
Bone morphogenetic protein 2 (BMP2)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary The overexpression of ALKBH5 led to the activation of p-AKT, and Bone morphogenetic protein 2 (BMP2) was regulated by ALKBH5 through the AKT signaling pathway. ALKBH5 promoted the osteogenesis of the ligamentum flavum cells through BMP2 demethylation and AKT activation. MK22606 is an AKT inhibitor. Moreover, when ALKBH5 was knocked down in the ligamentum flavum cells, p-AKT was inhibited when compared with that in the overexpressed ALKBH5 and control groups.
Responsed Disease Ossification of spinal ligaments [ICD-11: FA83]
Responsed Drug MK22606 Investigative
 Drug Info 
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
Target Regulation Up regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Ossification
In-vitro Model Ligamentum flavum cells (Ligamentum flavum cells)
RAC-alpha serine/threonine-protein kinase (AKT1)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary The overexpression of ALKBH5 led to the activation of RAC-alpha serine/threonine-protein kinase (AKT1), and BMP2 was regulated by ALKBH5 through the AKT signaling pathway. ALKBH5 promoted the osteogenesis of the ligamentum flavum cells through BMP2 demethylation and AKT activation. MK22606 is an AKT inhibitor. Moreover, when ALKBH5 was knocked down in the ligamentum flavum cells, p-AKT was inhibited when compared with that in the overexpressed ALKBH5 and control groups.
Responsed Disease Ossification of spinal ligaments [ICD-11: FA83]
Responsed Drug MK22606 Investigative
 Drug Info 
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
Target Regulation Up regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Ossification
In-vitro Model Ligamentum flavum cells (Ligamentum flavum cells)
X inactive specific transcript (XIST)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [4]
Response Summary METTL3 regulates ossification of the posterior longitudinal ligament via the lncRNA X inactive specific transcript (XIST)/miR-302a-3p/USP8 axis.
Responsed Disease Ossification of spinal ligaments [ICD-11: FA83]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Ubiquitin mediated proteolysis hsa04120
Cell Process Ubiquitination degradation
In-vitro Model Human primary ligament fibroblasts (Ligaments were dissected from a non-ossified site)
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: M6ACROT02052
 Crosstalk Info 
m6A Regulator Fat mass and obesity-associated protein (FTO)
 Regulator Info 
m6A Target Suppressor of cytokine signaling 3 (SOCS3)
 Target Gene 
Epigenetic Regulator DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target FTO alpha-ketoglutarate dependent dioxygenase (FTO)
Crosstalk relationship DNA modification → m6A
Crosstalk ID: M6ACROT03044
 Crosstalk Info 
m6A Regulator Methyltransferase-like 3 (METTL3)
 Regulator Info 
m6A Target Bone morphogenetic protein 2 (BMP2)
 Target Gene 
Epigenetic Regulator Lactate dehydrogenase A (LDHA)
Regulated Target Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship Histone modification → m6A
Crosstalk ID: M6ACROT03045
 Crosstalk Info 
m6A Regulator Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)
 Regulator Info 
m6A Target Bone morphogenetic protein 2 (BMP2)
 Target Gene 
Epigenetic Regulator Lactate dehydrogenase A (LDHA)
Regulated Target Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship Histone modification → m6A
Crosstalk ID: M6ACROT03306
 Crosstalk Info 
m6A Regulator Methyltransferase-like 3 (METTL3)
 Regulator Info 
m6A Target X inactive specific transcript (XIST)
 Target Gene 
Regulated Target Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship Histone modification → m6A
Crosstalk ID: M6ACROT05486
 Crosstalk Info 
m6A Regulator Methyltransferase-like 3 (METTL3)
 Regulator Info 
m6A Target X inactive specific transcript (XIST)
 Target Gene 
Epigenetic Regulator X inactive specific transcript (XIST)
Regulated Target hsa-miR-302a-3p
Crosstalk relationship m6A → ncRNA
References
Ref 1 BMP2 Modified by the m(6)A Demethylation Enzyme ALKBH5 in the Ossification of the Ligamentum Flavum Through the AKT Signaling Pathway. Calcif Tissue Int. 2020 May;106(5):486-493. doi: 10.1007/s00223-019-00654-6. Epub 2020 Jan 2.
Ref 2 Biochemical characterization of TAK-593, a novel VEGFR/PDGFR inhibitor with a two-step slow binding mechanism. Biochemistry. 2011 Feb 8;50(5):738-51. doi: 10.1021/bi101777f. Epub 2011 Jan 10.
Ref 3 PD-1 as a potential target in cancer therapy. Cancer Med. 2013 October; 2(5): 662-673.
Ref 4 METTL3 Regulates Ossification of the Posterior Longitudinal Ligament via the lncRNA XIST/miR-302a-3p/USP8 Axis. Front Cell Dev Biol. 2021 Mar 5;9:629895. doi: 10.3389/fcell.2021.629895. eCollection 2021.