m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00259)
Target Name Forkhead box protein O1 (FOXO1)
Synonyms
Forkhead box protein O1A; Forkhead in rhabdomyosarcoma; FKHR; FOXO1A
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Gene Name FOXO1
Chromosomal Location 13q14.11
Function
Transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress. Binds to the insulin response element (IRE) with consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16 family binding element (DBE) with consensus sequence 5'-TT[G/A]TTTAC-3' . Activity suppressed by insulin. Main regulator of redox balance and osteoblast numbers and controls bone mass (By similarity). Orchestrates the endocrine function of the skeleton in regulating glucose metabolism (By similarity). Also acts as a key regulator of chondrogenic commitment of skeletal progenitor cells in response to lipid availability: when lipids levels are low, translocates to the nucleus and promotes expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation (By similarity). Acts synergistically with ATF4 to suppress osteocalcin/BGLAP activity, increasing glucose levels and triggering glucose intolerance and insulin insensitivity (By similarity). Also suppresses the transcriptional activity of RUNX2, an upstream activator of osteocalcin/BGLAP (By similarity). In hepatocytes, promotes gluconeogenesis by acting together with PPARGC1A and CEBPA to activate the expression of genes such as IGFBP1, G6PC1 and PCK1 (By similarity). Important regulator of cell death acting downstream of CDK1, PKB/AKT1 and STK4/MST1. Promotes neural cell death. Mediates insulin action on adipose tissue (By similarity). Regulates the expression of adipogenic genes such as PPARG during preadipocyte differentiation and, adipocyte size and adipose tissue-specific gene expression in response to excessive calorie intake (By similarity). Regulates the transcriptional activity of GADD45A and repair of nitric oxide-damaged DNA in beta-cells (By similarity). Required for the autophagic cell death induction in response to starvation or oxidative stress in a transcription-independent manner. Mediates the function of MLIP in cardiomyocytes hypertrophy and cardiac remodeling (By similarity). Regulates endothelial cell (EC) viability and apoptosis in a PPIA/CYPA-dependent manner via transcription of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis.
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Gene ID 2308
Uniprot ID
FOXO1_HUMAN
HGNC ID
HGNC:3819
Ensembl Gene ID
ENSG00000150907
KEGG ID
hsa:2308
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
FOXO1 can be regulated by the following regulator(s), and cause disease/drug response(s). You can browse detail information of regulator(s) or disease/drug response(s).
Browse Regulator
Browse Disease
Methyltransferase-like 14 (METTL14) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL14
Cell Line MDA-MB-231 Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells
Control: MDA-MB-231 cells
 GSE81164
Regulation
logFC: -7.56E-01
p-value: 2.27E-07
More Results Click to View More RNA-seq Results
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary METTL14 promotes Forkhead box protein O1 (FOXO1) expression by enhancing its m6A modification and inducing endothelial cell inflammatory response as well as atherosclerotic plaque formation.
Target Regulation Up regulation
Responsed Disease Herpes infection ICD-11: 1F00
 Disease Info 
Pathway Response FoxO signaling pathway hsa04068
In-vitro Model HUVEC-C Normal Homo sapiens CVCL_2959
In-vivo Model METTL14+/- mice are generated by mating wild-type mice (C57/BL6 background) with METTL14+/- mice. METTL14+/-/APOE-/- healthy offspring mice are produced by heterozygous METTL14+/- mice and heterozygous APOE-/- mice by Mendelian ratios. APOE-/- mice and C57/BL6 mice were purchased from Model Animal Research Center of Nanjing (Nanjing, Jiangsu, China). All mice were housed in the Laboratory Animals Center of the Henan Provincial People's Hospital, with controlled temperature and humidity and a 12:12-hour dark-light cycle, and were provided water and mouse chow ad libitum.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary METTL14 promotes Forkhead box protein O1 (FOXO1) expression by enhancing its m6A modification and inducing endothelial cell inflammatory response as well as atherosclerotic plaque formation.
Target Regulation Up regulation
Responsed Disease Atherosclerosis ICD-11: BD40.Z
 Disease Info 
Pathway Response FoxO signaling pathway hsa04068
In-vitro Model HUVEC-C Normal Homo sapiens CVCL_2959
In-vivo Model Mettl14-/+ mice are generated by mating wild-type mice (C57/BL6 background) with Mettl14-/+ mice. Mettl14-/+/APOE-/- healthy offspring mice are produced by heterozygous Mettl14-/+ mice and heterozygous APOE-/- mice by Mendelian ratios. APOE-/- mice and C57/BL6 mice were purchased from Model Animal Research Center of Nanjing (Nanjing, Jiangsu, China). All mice were housed in the Laboratory Animals Center of the Henan Provincial People's Hospital, with controlled temperature and humidity and a 12:12-hour dark-light cycle, and were provided water and mouse chow ad libitum.
Methyltransferase-like 3 (METTL3) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line mouse embryonic stem cells Mus musculus
Treatment: METTL3-/- ESCs
Control: Wild type ESCs
 GSE145309
Regulation
logFC: 9.70E-01
p-value: 7.07E-55
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary Type 2 diabetes (T2D) is characterized by lack of insulin, insulin resistance and high blood sugar. METTL3 silence decreased the m6A methylated and total mRNA level of Fatty acid synthase (Fasn), subsequently inhibited fatty acid metabolism. The expression of Acc1, Acly, Dgat2, Ehhadh, Fasn, Forkhead box protein O1 (FOXO1), Pgc1a and Sirt1, which are critical to the regulation of fatty acid synthesis and oxidation were dramatically decreased in livers of hepatocyte-specific METTL3 knockout mice.
Target Regulation Up regulation
Responsed Disease Type 2 diabetes mellitus ICD-11: 5A11
 Disease Info 
Pathway Response Insulin resistance hsa04931
Cell Process Lipid metabolism
In-vitro Model Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
In-vivo Model Hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were generated by crossing mice with TBG-Cre Tg mice. METTL3 flox (METTL3 fl/fl) and hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were used for experiments.
Fat mass and obesity-associated protein (FTO) [ERASER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary Glucose Is Involved in the Dynamic Regulation of m6A in Patients with Type 2 Diabetes. High-glucose stimulation enhances FTO expression, which leads to decreased m6A, and the lower m6A induces methyltransferase upregulation; FTO then triggers the mRNA expression of Forkhead box protein O1 (FOXO1), FASN, G6PC, and DGAT2, and these four genes were correlated with glucose and lipid metabolism.
Responsed Disease Diabetes ICD-11: 5A10-5A14
 Disease Info 
Cell Process Lipid metabolism
In-vitro Model Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Herpes infection [ICD-11: 1F00]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary METTL14 promotes Forkhead box protein O1 (FOXO1) expression by enhancing its m6A modification and inducing endothelial cell inflammatory response as well as atherosclerotic plaque formation.
Responsed Disease Herpes infection [ICD-11: 1F00]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response FoxO signaling pathway hsa04068
In-vitro Model HUVEC-C Normal Homo sapiens CVCL_2959
In-vivo Model METTL14+/- mice are generated by mating wild-type mice (C57/BL6 background) with METTL14+/- mice. METTL14+/-/APOE-/- healthy offspring mice are produced by heterozygous METTL14+/- mice and heterozygous APOE-/- mice by Mendelian ratios. APOE-/- mice and C57/BL6 mice were purchased from Model Animal Research Center of Nanjing (Nanjing, Jiangsu, China). All mice were housed in the Laboratory Animals Center of the Henan Provincial People's Hospital, with controlled temperature and humidity and a 12:12-hour dark-light cycle, and were provided water and mouse chow ad libitum.
Diabetes [ICD-11: 5A10-5A14]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary Glucose Is Involved in the Dynamic Regulation of m6A in Patients with Type 2 Diabetes. High-glucose stimulation enhances FTO expression, which leads to decreased m6A, and the lower m6A induces methyltransferase upregulation; FTO then triggers the mRNA expression of Forkhead box protein O1 (FOXO1), FASN, G6PC, and DGAT2, and these four genes were correlated with glucose and lipid metabolism.
Responsed Disease Diabetes [ICD-11: 5A10-5A14]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Cell Process Lipid metabolism
In-vitro Model Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Type 2 diabetes mellitus [ICD-11: 5A11]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary Type 2 diabetes (T2D) is characterized by lack of insulin, insulin resistance and high blood sugar. METTL3 silence decreased the m6A methylated and total mRNA level of Fatty acid synthase (Fasn), subsequently inhibited fatty acid metabolism. The expression of Acc1, Acly, Dgat2, Ehhadh, Fasn, Forkhead box protein O1 (FOXO1), Pgc1a and Sirt1, which are critical to the regulation of fatty acid synthesis and oxidation were dramatically decreased in livers of hepatocyte-specific METTL3 knockout mice.
Responsed Disease Type 2 diabetes mellitus [ICD-11: 5A11]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Insulin resistance hsa04931
Cell Process Lipid metabolism
In-vitro Model Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
In-vivo Model Hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were generated by crossing mice with TBG-Cre Tg mice. METTL3 flox (METTL3 fl/fl) and hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were used for experiments.
Atherosclerosis [ICD-11: BD40]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary METTL14 promotes Forkhead box protein O1 (FOXO1) expression by enhancing its m6A modification and inducing endothelial cell inflammatory response as well as atherosclerotic plaque formation.
Responsed Disease Atherosclerosis [ICD-11: BD40.Z]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response FoxO signaling pathway hsa04068
In-vitro Model HUVEC-C Normal Homo sapiens CVCL_2959
In-vivo Model Mettl14-/+ mice are generated by mating wild-type mice (C57/BL6 background) with Mettl14-/+ mice. Mettl14-/+/APOE-/- healthy offspring mice are produced by heterozygous Mettl14-/+ mice and heterozygous APOE-/- mice by Mendelian ratios. APOE-/- mice and C57/BL6 mice were purchased from Model Animal Research Center of Nanjing (Nanjing, Jiangsu, China). All mice were housed in the Laboratory Animals Center of the Henan Provincial People's Hospital, with controlled temperature and humidity and a 12:12-hour dark-light cycle, and were provided water and mouse chow ad libitum.
References
Ref 1 METTL14 aggravates endothelial inflammation and atherosclerosis by increasing FOXO1 N6-methyladeosine modifications. Theranostics. 2020 Jul 11;10(20):8939-8956. doi: 10.7150/thno.45178. eCollection 2020.
Ref 2 METTL3 inhibits hepatic insulin sensitivity via N6-methyladenosine modification of Fasn mRNA and promoting fatty acid metabolism. Biochem Biophys Res Commun. 2019 Oct 8;518(1):120-126. doi: 10.1016/j.bbrc.2019.08.018. Epub 2019 Aug 10.
Ref 3 Glucose Is Involved in the Dynamic Regulation of m6A in Patients With Type 2 Diabetes. J Clin Endocrinol Metab. 2019 Mar 1;104(3):665-673. doi: 10.1210/jc.2018-00619.