m6A-centered Disease Response Information

General Information of the Disease (ID: M6ADIS0124)
Name
Human skin lesions
ICD
ICD-11: ME60
Full List of Target Gene(s) of This m6A-centered Disease Response
E3 ubiquitin-protein ligase NEDD4-like (NEDD4L)
 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 FTO deletion inhibited arsenic-induced tumorigenesis. Epidermis-specific FTO deletion prevented skin tumorigenesis induced by arsenic and UVB irradiation. E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) was identified as the m6A-modified gene target of FTO. Arsenic stabilizes FTO protein through inhibiting p62-mediated selective autophagy. FTO-mediated dysregulation of mRNA m6A methylation as an epitranscriptomic mechanism to promote arsenic tumorigenicity. Arsenic suppresses p62 expression by downregulating the NF-kappaB pathway to upregulate FTO.
Responsed Disease Human skin lesions [ICD-11: ME60]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Pathway Response Autophagy hsa04140
Cell Process Cellular Processes
Transport and catabolism
Cell autophagy
In-vitro Model HaCaT Normal Homo sapiens CVCL_0038
HEK293T Normal Homo sapiens CVCL_0063
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
MEF (Mouse embryonic fibroblasts)
In-vivo Model As cells (5 million) in Matrigel or As-T (1 million) cells in PBS with or without gene manipulations were injected subcutaneously into the right flanks of female mice (6-8 weeks of age). For treatment with CS1 or CS2, As-T cells (1 million) in PBS were injected subcutaneously into the right flanks of 6-week-old female nude mice.
Sequestosome-1 (SQSTM1)
 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 FTO deletion inhibited arsenic-induced tumorigenesis. Epidermis-specific FTO deletion prevented skin tumorigenesis induced by arsenic and UVB irradiation. NEDD4L was identified as the m6A-modified gene target of FTO. Arsenic stabilizes FTO protein through inhibiting Sequestosome-1 (SQSTM1)-mediated selective autophagy. FTO-mediated dysregulation of mRNA m6A methylation as an epitranscriptomic mechanism to promote arsenic tumorigenicity. Arsenic suppresses p62 expression by downregulating the NF-kappaB pathway to upregulate FTO.
Responsed Disease Human skin lesions [ICD-11: ME60]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Down regulation
Pathway Response Autophagy hsa04140
Cell Process Cellular Processes
Transport and catabolism
Cell autophagy
In-vitro Model HaCaT Normal Homo sapiens CVCL_0038
HEK293T Normal Homo sapiens CVCL_0063
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
MEF (Mouse embryonic fibroblasts)
In-vivo Model As cells (5 million) in Matrigel or As-T (1 million) cells in PBS with or without gene manipulations were injected subcutaneously into the right flanks of female mice (6-8 weeks of age). For treatment with CS1 or CS2, As-T cells (1 million) in PBS were injected subcutaneously into the right flanks of 6-week-old female nude mice.
References
Ref 1 Autophagy of the m(6)A mRNA demethylase FTO is impaired by low-level arsenic exposure to promote tumorigenesis. Nat Commun. 2021 Apr 12;12(1):2183. doi: 10.1038/s41467-021-22469-6.
Ref 2 Discovery of cyclic amine-substituted benzoic acids as PPARAlpha agonists. Bioorg Med Chem Lett. 2012 Jan 1;22(1):334-8. doi: 10.1016/j.bmcl.2011.11.002. Epub 2011 Nov 9.