m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00418)
Target Name Signal transducer and activator of transcription 3 (STAT3)
Synonyms
Acute-phase response factor; APRF
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Gene Name STAT3
Chromosomal Location 17q21.2
Family transcription factor STAT family
Function
Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Upon activation of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-responsive elements identified in the promoters of various acute-phase protein genes. Activated by IL31 through IL31RA. Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg): deacetylation and oxidation of lysine residues by LOXL3, leads to disrupt STAT3 dimerization and inhibit its transcription activity. Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1. Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation (By similarity). May play an apoptotic role by transctivating BIRC5 expression under LEP activation. Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity. Plays a crucial role in basal beta cell functions, such as regulation of insulin secretion (By similarity).
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Gene ID 6774
Uniprot ID
STAT3_HUMAN
HGNC ID
HGNC:11364
Ensembl Gene ID
ENSG00000168610
KEGG ID
hsa:6774
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
STAT3 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).
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Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) [READER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by IGF2BP1
Cell Line ES-2 cell line Homo sapiens
Treatment: siIGF2BP1 ES-2 cells
Control: siControl ES-2 cells
 GSE161087
Regulation
logFC: 6.53E-01
p-value: 9.70E-05
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 METTL3 knockdown prevented Atherosclerosis progression by inhibiting JAK2/Signal transducer and activator of transcription 3 (STAT3) pathway via IGF2BP1.
Target Regulation Up regulation
Responsed Disease Atherosclerosis ICD-11: BD40.Z
 Disease Info 
Pathway Response JAK-STAT signaling pathway hsa04630
Cell Process Cell proliferation and migration
In-vitro Model HUVEC-C Normal Homo sapiens CVCL_2959
In-vivo Model The adeno-associated viruses (AAV) that could silence METTL3 (sh-METTL3) and the negative control adeno-associated viruses (sh-NC) were obtained from WZ Biosciences Inc. (Jinan, China). APOE-/- mice were randomly divided into AS + sh-NC and AS + sh-METTL3 groups. Each group contains five mice. Mice were fed with the standard diet for 1 week to acclimatize. After 1 week of acclimation, mice were challenged with a high-fat and high-cholesterol feed H10540 (Beijing HFK BIOSCIENCE Co., Ltd., Beijing, China). The formula of the H10540 feed was shown in Supplementary File S1. After 8 weeks of HFD feeding, sh-NC or sh-METTL3 adeno-associated virus serotype 9 (AAV9, 1012 viral genome copies per mouse) were respectively delivered into mice in AS + sh-NC or AS + sh-METTL3 group through tail vein injection. At 14 weeks after HDF feeding, mice fasted overnight.
Methyltransferase-like 3 (METTL3) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line Embryonic stem cells Mus musculus
Treatment: METTL3 knockout mESCs
Control: Wild type mESCs
 GSE156481
Regulation
logFC: -6.99E-01
p-value: 1.19E-15
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 METTL3 knockdown prevented Atherosclerosis progression by inhibiting JAK2/Signal transducer and activator of transcription 3 (STAT3) pathway via IGF2BP1.
Target Regulation Up regulation
Responsed Disease Atherosclerosis ICD-11: BD40.Z
 Disease Info 
Pathway Response JAK-STAT signaling pathway hsa04630
Cell Process Cell proliferation and migration
In-vitro Model HUVEC-C Normal Homo sapiens CVCL_2959
In-vivo Model The adeno-associated viruses (AAV) that could silence METTL3 (sh-METTL3) and the negative control adeno-associated viruses (sh-NC) were obtained from WZ Biosciences Inc. (Jinan, China). APOE-/- mice were randomly divided into AS + sh-NC and AS + sh-METTL3 groups. Each group contains five mice. Mice were fed with the standard diet for 1 week to acclimatize. After 1 week of acclimation, mice were challenged with a high-fat and high-cholesterol feed H10540 (Beijing HFK BIOSCIENCE Co., Ltd., Beijing, China). The formula of the H10540 feed was shown in Supplementary File S1. After 8 weeks of HFD feeding, sh-NC or sh-METTL3 adeno-associated virus serotype 9 (AAV9, 1012 viral genome copies per mouse) were respectively delivered into mice in AS + sh-NC or AS + sh-METTL3 group through tail vein injection. At 14 weeks after HDF feeding, mice fasted overnight.
RNA demethylase ALKBH5 (ALKBH5) [ERASER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5
Cell Line 143B cell line Homo sapiens
Treatment: siALKBH5 transfected 143B cells
Control: siControl 143B cells
 GSE154528
Regulation
logFC: 1.23E+00
p-value: 2.84E-10
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 ALKBH5 inactivated Signal transducer and activator of transcription 3 (STAT3) pathway by increasing SOCS3 expression via an m6A-YTHDF2-dependent manner. Reducing m6A mRNA levels in human osteosarcoma cells through ALKBH5 up-regulation lead to cell proliferation inhibition, cell apoptosis and cycle arrest.
Target Regulation Down regulation
Responsed Disease Osteosarcoma ICD-11: 2B51
 Disease Info 
Pathway Response JAK-STAT signaling pathway hsa04630
In-vitro Model U2OS Osteosarcoma Homo sapiens CVCL_0042
OS3 [Human osteosarcoma] Osteosarcoma Homo sapiens CVCL_F866
OS2 [Human osteosarcoma] Osteosarcoma Homo sapiens CVCL_F865
OS1 [Human osteosarcoma] Osteosarcoma Homo sapiens CVCL_F864
KHOS/NP Osteosarcoma Homo sapiens CVCL_2546
YTH domain-containing family protein 2 (YTHDF2) [READER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2
Cell Line GSC11 cell line Homo sapiens
Treatment: siYTHDF2 GSC11 cells
Control: siControl GSC11 cells
 GSE142825
Regulation
logFC: -6.33E-01
p-value: 6.04E-06
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 ALKBH5 inactivated Signal transducer and activator of transcription 3 (STAT3) pathway by increasing SOCS3 expression via an m6A-YTHDF2-dependent manner. Reducing m6A mRNA levels in human osteosarcoma cells through ALKBH5 up-regulation lead to cell proliferation inhibition, cell apoptosis and cycle arrest.
Target Regulation Down regulation
Responsed Disease Osteosarcoma ICD-11: 2B51
 Disease Info 
Pathway Response JAK-STAT signaling pathway hsa04630
In-vitro Model U2OS Osteosarcoma Homo sapiens CVCL_0042
OS3 [Human osteosarcoma] Osteosarcoma Homo sapiens CVCL_F866
OS2 [Human osteosarcoma] Osteosarcoma Homo sapiens CVCL_F865
OS1 [Human osteosarcoma] Osteosarcoma Homo sapiens CVCL_F864
KHOS/NP Osteosarcoma Homo sapiens CVCL_2546
Fat mass and obesity-associated protein (FTO) [ERASER]
 Regulator Info 
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary FTO inhibits adipocytes apoptosis via reducing m6A epigenetic modification-mediated UPRmt.UPRmt-induced increase in PKR and eIF2-alpha phosphorylation, and ATF5-mediated upregulation of BAX expression promoted apoptosis. Furthermore, adipocytes apoptosis is inhibited by FTO-activated JAK2/Signal transducer and activator of transcription 3 (STAT3) signaling pathway
Pathway Response Adipocytokine signaling pathway hsa04920
JAK-STAT signaling pathway hsa04630
Cell Process Mitochondria-dependent apoptosis
Cell apoptosis
In-vitro Model 3T3-L1 Normal Mus musculus CVCL_0123
In-vivo Model Mice were provided adlibitum with water and a standard laboratory chow diet. The animal room was held a standard temperature, humidity and illumination. After intraperitoneal injection of FTO overexpression vector and NR to mice for 7 days, inguinal white adipose tissue (iWAT) were collected from mice.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [4]
Response Summary Decreased doxorubicin resistance by Signal transducer and activator of transcription 3 (STAT3) knockdown was abolished by FTO overexpression and decreased doxorubicin sensitivity by STAT3 overexpression was reversed by FTO knockdown, indicating that FTO was implicated in STAT3-mediated doxorubicin resistance and impairment of doxorubicin sensitivity of BC cells.
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Drug Doxil Approved
 Drug Info 
In-vitro Model MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
Hs 578T Invasive breast carcinoma Homo sapiens CVCL_0332
Osteosarcoma [ICD-11: 2B51]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary ALKBH5 inactivated Signal transducer and activator of transcription 3 (STAT3) pathway by increasing SOCS3 expression via an m6A-YTHDF2-dependent manner. Reducing m6A mRNA levels in human osteosarcoma cells through ALKBH5 up-regulation lead to cell proliferation inhibition, cell apoptosis and cycle arrest.
Responsed Disease Osteosarcoma [ICD-11: 2B51]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
Target Regulation Down regulation
Pathway Response JAK-STAT signaling pathway hsa04630
In-vitro Model U2OS Osteosarcoma Homo sapiens CVCL_0042
OS3 [Human osteosarcoma] Osteosarcoma Homo sapiens CVCL_F866
OS2 [Human osteosarcoma] Osteosarcoma Homo sapiens CVCL_F865
OS1 [Human osteosarcoma] Osteosarcoma Homo sapiens CVCL_F864
KHOS/NP Osteosarcoma Homo sapiens CVCL_2546
Experiment 2 Reporting the m6A-centered Disease Response [2]
Response Summary ALKBH5 inactivated Signal transducer and activator of transcription 3 (STAT3) pathway by increasing SOCS3 expression via an m6A-YTHDF2-dependent manner. Reducing m6A mRNA levels in human osteosarcoma cells through ALKBH5 up-regulation lead to cell proliferation inhibition, cell apoptosis and cycle arrest.
Responsed Disease Osteosarcoma [ICD-11: 2B51]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Down regulation
Pathway Response JAK-STAT signaling pathway hsa04630
In-vitro Model U2OS Osteosarcoma Homo sapiens CVCL_0042
OS3 [Human osteosarcoma] Osteosarcoma Homo sapiens CVCL_F866
OS2 [Human osteosarcoma] Osteosarcoma Homo sapiens CVCL_F865
OS1 [Human osteosarcoma] Osteosarcoma Homo sapiens CVCL_F864
KHOS/NP Osteosarcoma Homo sapiens CVCL_2546
Breast cancer [ICD-11: 2C60]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [4]
Response Summary Decreased doxorubicin resistance by Signal transducer and activator of transcription 3 (STAT3) knockdown was abolished by FTO overexpression and decreased doxorubicin sensitivity by STAT3 overexpression was reversed by FTO knockdown, indicating that FTO was implicated in STAT3-mediated doxorubicin resistance and impairment of doxorubicin sensitivity of BC cells.
Responsed Disease Breast cancer [ICD-11: 2C60]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Responsed Drug Doxil Approved
 Drug Info 
In-vitro Model MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
Hs 578T Invasive breast carcinoma Homo sapiens CVCL_0332
Atherosclerosis [ICD-11: BD40]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary METTL3 knockdown prevented Atherosclerosis progression by inhibiting JAK2/Signal transducer and activator of transcription 3 (STAT3) pathway via IGF2BP1.
Responsed Disease Atherosclerosis [ICD-11: BD40.Z]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response JAK-STAT signaling pathway hsa04630
Cell Process Cell proliferation and migration
In-vitro Model HUVEC-C Normal Homo sapiens CVCL_2959
In-vivo Model The adeno-associated viruses (AAV) that could silence METTL3 (sh-METTL3) and the negative control adeno-associated viruses (sh-NC) were obtained from WZ Biosciences Inc. (Jinan, China). APOE-/- mice were randomly divided into AS + sh-NC and AS + sh-METTL3 groups. Each group contains five mice. Mice were fed with the standard diet for 1 week to acclimatize. After 1 week of acclimation, mice were challenged with a high-fat and high-cholesterol feed H10540 (Beijing HFK BIOSCIENCE Co., Ltd., Beijing, China). The formula of the H10540 feed was shown in Supplementary File S1. After 8 weeks of HFD feeding, sh-NC or sh-METTL3 adeno-associated virus serotype 9 (AAV9, 1012 viral genome copies per mouse) were respectively delivered into mice in AS + sh-NC or AS + sh-METTL3 group through tail vein injection. At 14 weeks after HDF feeding, mice fasted overnight.
Experiment 2 Reporting the m6A-centered Disease Response [1]
Response Summary METTL3 knockdown prevented Atherosclerosis progression by inhibiting JAK2/Signal transducer and activator of transcription 3 (STAT3) pathway via IGF2BP1.
Responsed Disease Atherosclerosis [ICD-11: BD40.Z]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response JAK-STAT signaling pathway hsa04630
Cell Process Cell proliferation and migration
In-vitro Model HUVEC-C Normal Homo sapiens CVCL_2959
In-vivo Model The adeno-associated viruses (AAV) that could silence METTL3 (sh-METTL3) and the negative control adeno-associated viruses (sh-NC) were obtained from WZ Biosciences Inc. (Jinan, China). APOE-/- mice were randomly divided into AS + sh-NC and AS + sh-METTL3 groups. Each group contains five mice. Mice were fed with the standard diet for 1 week to acclimatize. After 1 week of acclimation, mice were challenged with a high-fat and high-cholesterol feed H10540 (Beijing HFK BIOSCIENCE Co., Ltd., Beijing, China). The formula of the H10540 feed was shown in Supplementary File S1. After 8 weeks of HFD feeding, sh-NC or sh-METTL3 adeno-associated virus serotype 9 (AAV9, 1012 viral genome copies per mouse) were respectively delivered into mice in AS + sh-NC or AS + sh-METTL3 group through tail vein injection. At 14 weeks after HDF feeding, mice fasted overnight.
Doxil [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [4]
Response Summary Decreased doxorubicin resistance by Signal transducer and activator of transcription 3 (STAT3) knockdown was abolished by FTO overexpression and decreased doxorubicin sensitivity by STAT3 overexpression was reversed by FTO knockdown, indicating that FTO was implicated in STAT3-mediated doxorubicin resistance and impairment of doxorubicin sensitivity of BC cells.
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
In-vitro Model MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
Hs 578T Invasive breast carcinoma Homo sapiens CVCL_0332
References
Ref 1 N6-Methyladenosine Methyltransferase METTL3 Promotes Angiogenesis and Atherosclerosis by Upregulating the JAK2/STAT3 Pathway via m6A Reader IGF2BP1. Front Cell Dev Biol. 2021 Dec 7;9:731810. doi: 10.3389/fcell.2021.731810. eCollection 2021.
Ref 2 ALKBH5 regulates STAT3 activity to affect the proliferation and tumorigenicity of osteosarcoma via an m6A-YTHDF2-dependent manner. EBioMedicine. 2022 Jun;80:104019. doi: 10.1016/j.ebiom.2022.104019. Epub 2022 Apr 28.
Ref 3 FTO inhibits UPR(mt)-induced apoptosis by activating JAK2/STAT3 pathway and reducing m6A level in adipocytes. Apoptosis. 2021 Aug;26(7-8):474-487. doi: 10.1007/s10495-021-01683-z. Epub 2021 Jul 1.
Ref 4 Fat mass and obesity-associated protein (FTO) mediates signal transducer and activator of transcription 3 (STAT3)-drived resistance of breast cancer to doxorubicin. Bioengineered. 2021 Dec;12(1):1874-1889. doi: 10.1080/21655979.2021.1924544.