m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00738)
Target Name Mothers against decapentaplegic homolog 6 (SMAD6)
Synonyms
MAD homolog 6; Mothers against DPP homolog 6; SMAD family member 6; SMAD 6; Smad6; hSMAD6
    Click to Show/Hide
Gene Name SMAD6
Chromosomal Location 15q22.31
Family Dwarfin/SMAD family
Function
Transforming growth factor-beta superfamily receptors signaling occurs through the Smad family of intracellular mediators. SMAD6 is an inhibitory Smad (i-Smad) that negatively regulates signaling downstream of type I transforming growth factor-beta. Acts as a mediator of TGF-beta and BMP anti-inflammatory activities. Suppresses IL1R-TLR signaling through its direct interaction with PEL1, preventing NF-kappa-B activation, nuclear transport and NF-kappa-B-mediated expression of pro-inflammatory genes. Blocks the BMP-SMAD1 signaling pathway by competing with SMAD4 for receptor-activated SMAD1-binding . Binds to regulatory elements in target promoter regions.
    Click to Show/Hide
Gene ID 4091
Uniprot ID
SMAD6_HUMAN
HGNC ID
HGNC:6772
Ensembl Gene ID
ENSG00000137834
KEGG ID
hsa:4091
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
SMAD6 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
RNA demethylase ALKBH5 (ALKBH5) [ERASER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5
Cell Line THP1 cell line Homo sapiens
Treatment: ALKBH5 knockdown THP1 cells
Control: Wild type THP1 cells
 GSE128574
Regulation
logFC: 7.02E-01
p-value: 2.75E-03
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 ALKBH5 weakens YTHDF1/3-mediated TGF-Beta-R2 and SMAD3 mRNA stabilization, and abolishes YTHDF2-mediated Mothers against decapentaplegic homolog 6 (SMAD6) mRNA degradation, supporting the notion that ALKBH5 inhibits TGF-Beta-induced EMT and invasion of NSCLC cells via YTHD1/2/3-mediated mechanism.
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Pathway Response TGF-beta signaling pathway hsa04350
Cell Process Epithelial-mesenchymal transition
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
NCI-H1650 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1483
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
In-vivo Model The mice were divided into control group and ALKBH5-overexpressing group (9 mice per group). ALKBH5-overexpressing and control A549 cells (3 × 106 cells/mouse) in 200 uL PBS were intravenously (i.v.) injected into the lateral tail vein of mice. At every 5th day post-inoculation, TGF-Beta-1 (4 ug/kg body weight) was intraperitoneally (i.p.) injected to promote tumor cell metastasis. Eight weeks later, the mice were euthanized, and then their lungs and livers were taken out and fixed in Bouin's solution (Sigma Aldrich, HT101128) or 4% Paraformaldehyde (Beyotime, p0099, Shanghai, China) for macroscopically metastatic nodule analysis.
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary ALKBH5 weakens YTHDF1/3-mediated TGF-Beta-R2 and SMAD3 mRNA stabilization, and abolishes YTHDF2-mediated Mothers against decapentaplegic homolog 6 (SMAD6) mRNA degradation, supporting the notion that ALKBH5 inhibits TGF-Beta-induced EMT and invasion of NSCLC cells via YTHD1/2/3-mediated mechanism.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
Target Regulation Up regulation
Pathway Response TGF-beta signaling pathway hsa04350
Cell Process Epithelial-mesenchymal transition
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
NCI-H1650 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1483
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
In-vivo Model The mice were divided into control group and ALKBH5-overexpressing group (9 mice per group). ALKBH5-overexpressing and control A549 cells (3 × 106 cells/mouse) in 200 uL PBS were intravenously (i.v.) injected into the lateral tail vein of mice. At every 5th day post-inoculation, TGF-Beta-1 (4 ug/kg body weight) was intraperitoneally (i.p.) injected to promote tumor cell metastasis. Eight weeks later, the mice were euthanized, and then their lungs and livers were taken out and fixed in Bouin's solution (Sigma Aldrich, HT101128) or 4% Paraformaldehyde (Beyotime, p0099, Shanghai, China) for macroscopically metastatic nodule analysis.
References
Ref 1 RNA demethylase ALKBH5 inhibits TGF-Beta-induced EMT by regulating TGF-Beta/SMAD signaling in non-small cell lung?cancer. FASEB J. 2022 May;36(5):e22283. doi: 10.1096/fj.202200005RR.