m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00169)
Target Name ATP-citrate synthase (ACLY)
Synonyms
ATP-citrate (pro-S-)-lyase; ACL; Citrate cleavage enzyme
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Gene Name ACLY
Chromosomal Location 17q21.2
Family succinate/malate CoA ligase beta subunit family
Function
Catalyzes the cleavage of citrate into oxaloacetate and acetyl-CoA, the latter serving as common substrate for de novo cholesterol and fatty acid synthesis.
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Gene ID 47
Uniprot ID
ACLY_HUMAN
HGNC ID
HGNC:115
Ensembl Gene ID
ENSG00000131473
KEGG ID
hsa:47
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
ACLY 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
Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) [READER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by HNRNPA2B1
Cell Line HeLa cell line Homo sapiens
Treatment: HNRNPA2B1 knockdown HeLa cells
Control: HeLa cells
 GSE70061
Regulation
logFC: 7.79E-01
p-value: 2.27E-02
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 [1]
Response Summary The levels of m6A and its regulator HNRNPA2B1 were significantly increased in cancerous tissues of esophageal cancer(ESCA), and overexpression of HNRNPA2B1 promotes ESCA progression via up-regulation of de novo fatty acid synthetic enzymes ATP-citrate synthase (ACLY) and ACC1.
Target Regulation Up regulation
Responsed Disease Esophageal cancer ICD-11: 2B70
 Disease Info 
Pathway Response Metabolic pathways hsa01100
Cell Process Fatty acid synthesis
In-vitro Model TE-10 Esophageal squamous cell carcinoma Homo sapiens CVCL_1760
Eca-109 Esophageal squamous cell carcinoma Homo sapiens CVCL_6898
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: 7.95E-01
p-value: 2.66E-12
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 Targeting METTL3/14 in vitro increases protein level of ATP-citrate synthase (ACLY) and SCD1 as well as triglyceride and cholesterol production and accumulation of lipid droplets. These findings demonstrate a new NAFLD mouse model that provides a study platform for DM2-related NAFLD and reveals a unique epitranscriptional regulating mechanism for lipid metabolism via m6A-modified protein expression of ACLY and SCD1.
Target Regulation Up regulation
Responsed Disease Non-alcoholic fatty liver disease ICD-11: DB92
 Disease Info 
Pathway Response Glycerolipid metabolism hsa00561
Cell Process Lipid metabolism
In-vitro Model LM3 Malignant neoplasms Mus musculus CVCL_D269
MHCC97-H Adult hepatocellular carcinoma Homo sapiens CVCL_4972
In-vivo Model Mice with a Tmem30a deletion specifically in pancreatic beta cells were generated as previously described. Mice developed with NAFLD were named for Tmem30a-associated NAFLD (TAN) mice. The littermate mice with genotypes of Tmem30aloxP/loxP were used as controls.
Methyltransferase-like 3 (METTL3) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line Liver Mus musculus
Treatment: Mettl3 knockout liver
Control: Wild type liver cells
 GSE198513
Regulation
logFC: -6.16E-01
p-value: 1.78E-18
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 [3]
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, ATP-citrate synthase (ACLY), Dgat2, Ehhadh, Fasn, Foxo, 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.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary Targeting METTL3/14 in vitro increases protein level of ATP-citrate synthase (ACLY) and SCD1 as well as triglyceride and cholesterol production and accumulation of lipid droplets. These findings demonstrate a new NAFLD mouse model that provides a study platform for DM2-related NAFLD and reveals a unique epitranscriptional regulating mechanism for lipid metabolism via m6A-modified protein expression of ACLY and SCD1.
Target Regulation Up regulation
Responsed Disease Non-alcoholic fatty liver disease ICD-11: DB92
 Disease Info 
Pathway Response Glycerolipid metabolism hsa00561
Cell Process Lipid metabolism
In-vitro Model LM3 Malignant neoplasms Mus musculus CVCL_D269
MHCC97-H Adult hepatocellular carcinoma Homo sapiens CVCL_4972
In-vivo Model Mice with a Tmem30a deletion specifically in pancreatic beta cells were generated as previously described. Mice developed with NAFLD were named for Tmem30a-associated NAFLD (TAN) mice. The littermate mice with genotypes of Tmem30aloxP/loxP were used as controls.
Esophageal cancer [ICD-11: 2B70]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary The levels of m6A and its regulator HNRNPA2B1 were significantly increased in cancerous tissues of esophageal cancer(ESCA), and overexpression of HNRNPA2B1 promotes ESCA progression via up-regulation of de novo fatty acid synthetic enzymes ATP-citrate synthase (ACLY) and ACC1.
Responsed Disease Esophageal cancer [ICD-11: 2B70]
Target Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Metabolic pathways hsa01100
Cell Process Fatty acid synthesis
In-vitro Model TE-10 Esophageal squamous cell carcinoma Homo sapiens CVCL_1760
Eca-109 Esophageal squamous cell carcinoma Homo sapiens CVCL_6898
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 [3]
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, ATP-citrate synthase (ACLY), Dgat2, Ehhadh, Fasn, Foxo, 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.
Non-alcoholic fatty liver disease [ICD-11: DB92]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary Targeting METTL3/14 in vitro increases protein level of ATP-citrate synthase (ACLY) and SCD1 as well as triglyceride and cholesterol production and accumulation of lipid droplets. These findings demonstrate a new NAFLD mouse model that provides a study platform for DM2-related NAFLD and reveals a unique epitranscriptional regulating mechanism for lipid metabolism via m6A-modified protein expression of ACLY and SCD1.
Responsed Disease Non-alcoholic fatty liver disease [ICD-11: DB92]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Glycerolipid metabolism hsa00561
Cell Process Lipid metabolism
In-vitro Model LM3 Malignant neoplasms Mus musculus CVCL_D269
MHCC97-H Adult hepatocellular carcinoma Homo sapiens CVCL_4972
In-vivo Model Mice with a Tmem30a deletion specifically in pancreatic beta cells were generated as previously described. Mice developed with NAFLD were named for Tmem30a-associated NAFLD (TAN) mice. The littermate mice with genotypes of Tmem30aloxP/loxP were used as controls.
References
Ref 1 m(6)A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1. Front Oncol. 2020 Sep 29;10:553045. doi: 10.3389/fonc.2020.553045. eCollection 2020.
Ref 2 Dysregulated m6A modification promotes lipogenesis and development of non-alcoholic fatty liver disease and hepatocellular carcinoma. Mol Ther. 2022 Jun 1;30(6):2342-2353. doi: 10.1016/j.ymthe.2022.02.021. Epub 2022 Feb 19.
Ref 3 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.