m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00310)
Target Name Krueppel-like factor 4 (KLF4)
Synonyms
Epithelial zinc finger protein EZF; Gut-enriched krueppel-like factor; EZF; GKLF
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Gene Name KLF4
Chromosomal Location 9q31.2
Family krueppel C2H2-type zinc-finger protein family
Function
Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3' core sequence. Binds to the promoter region of its own gene and can activate its own transcription. Regulates the expression of key transcription factors during embryonic development. Plays an important role in maintaining embryonic stem cells, and in preventing their differentiation. Required for establishing the barrier function of the skin and for postnatal maturation and maintenance of the ocular surface. Involved in the differentiation of epithelial cells and may also function in skeletal and kidney development. Contributes to the down-regulation of p53/TP53 transcription.
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Gene ID 9314
Uniprot ID
KLF4_HUMAN
HGNC ID
HGNC:6348
Ensembl Gene ID
ENSG00000136826
KEGG ID
hsa:9314
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
KLF4 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
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: 6.24E-01
p-value: 8.92E-03
More Results Click to View More RNA-seq Results
Representative RIP-seq result supporting the interaction between KLF4 and the regulator
Cell Line Hela Homo sapiens
Regulation logFC: 2.55E+00 GSE49339
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary miR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor Krueppel-like factor 4 (KLF4). miR-1915-3p function as a tumor suppressor by targeting SET and has an anti-metastatic therapeutic potential for lung cancer treatment.
Target Regulation Down regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Pathway Response TNF signaling pathway hsa04668
Cell Process Cell migration
Cell invasion
Epithelial-mesenchymal transition
In-vitro Model NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary METTL3/YTHDF2/SETD7/Krueppel-like factor 4 (KLF4) m6 A axis provide the insight into the underlying mechanism of carcinogenesis and highlight potential therapeutic targets for bladder cancer.
Target Regulation Down regulation
Responsed Disease Bladder cancer ICD-11: 2C94
 Disease Info 
Cell Process Cancer proliferation
Cancer metastasis
In-vitro Model SV-HUC-1 Normal Homo sapiens CVCL_3798
T24 Bladder carcinoma Homo sapiens CVCL_0554
UM-UC-3 Bladder carcinoma Homo sapiens CVCL_1783
In-vivo Model For the subcutaneous implantation model, UM-UC-3 cells (2 × 106 cells per mouse) stably METTL3 knocked down (shMETTL3-1, shMETTL3-2) were injected into the flanks of mice.
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: -8.55E-01
p-value: 7.89E-09
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 [3]
Response Summary The expression of METTL14 was downregulated in CRC cells and METTL14 could inhibit the metastasis of CRC cells. MeCP2 could bind to METTL14 to coregulate tumor suppressor Krueppel-like factor 4 (KLF4) expression through changing m6 A methylation modification.
Target Regulation Up regulation
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
In-vitro Model SW620 Colon adenocarcinoma Homo sapiens CVCL_0547
HT29 Colon cancer Mus musculus CVCL_A8EZ
HCT 8 Colon adenocarcinoma Homo sapiens CVCL_2478
In-vivo Model In vivo, the group of HCT116 cells labeled with luciferase were surgically injected into the spleen of nude mice. After 2 months, the nude mice were subjected to D-luciferin injection and the luciferase signals were monitored and quantified.
Methyltransferase-like 3 (METTL3) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line HUVEC cell line Homo sapiens
Treatment: shMETTL3 HUVEC cells
Control: shScramble HUVEC cells
 GSE157544
Regulation
logFC: -8.63E-01
p-value: 1.22E-04
More Results Click to View More RNA-seq Results
In total 3 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary miR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor Krueppel-like factor 4 (KLF4). miR-1915-3p function as a tumor suppressor by targeting SET and has an anti-metastatic therapeutic potential for lung cancer treatment.
Target Regulation Down regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Pathway Response TNF signaling pathway hsa04668
Cell Process Cell migration
Cell invasion
Epithelial-mesenchymal transition
In-vitro Model NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary METTL3/YTHDF2/SETD7/Krueppel-like factor 4 (KLF4) m6 A axis provide the insight into the underlying mechanism of carcinogenesis and highlight potential therapeutic targets for bladder cancer.
Target Regulation Down regulation
Responsed Disease Bladder cancer ICD-11: 2C94
 Disease Info 
Cell Process Cancer proliferation
Cancer metastasis
In-vitro Model SV-HUC-1 Normal Homo sapiens CVCL_3798
T24 Bladder carcinoma Homo sapiens CVCL_0554
UM-UC-3 Bladder carcinoma Homo sapiens CVCL_1783
In-vivo Model For the subcutaneous implantation model, UM-UC-3 cells (2 × 106 cells per mouse) stably METTL3 knocked down (shMETTL3-1, shMETTL3-2) were injected into the flanks of mice.
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [4]
Response Summary In the in vivo atherosclerosis model,partial ligation of the carotid artery led to plaque formation and up-regulation of METTL3 and NLRP1, with down-regulation of KLF4; knockdown of METTL3 via repetitive shRNA administration prevented the atherogenic process, NLRP1 up-regulation, and Krueppel-like factor 4 (KLF4) down-regulation. Collectively, it has demonstrated that METTL3 serves a central role in the atherogenesis induced by oscillatory stress and disturbed blood flow.
Target Regulation Down regulation
Responsed Disease Atherosclerosis ICD-11: BD40.Z
 Disease Info 
In-vitro Model MAEC Normal Mus musculus CVCL_U411
HUVEC-C Normal Homo sapiens CVCL_2959
Colorectal cancer [ICD-11: 2B91]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary The expression of METTL14 was downregulated in CRC cells and METTL14 could inhibit the metastasis of CRC cells. MeCP2 could bind to METTL14 to coregulate tumor suppressor Krueppel-like factor 4 (KLF4) expression through changing m6 A methylation modification.
Responsed Disease Colorectal cancer [ICD-11: 2B91]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Up regulation
In-vitro Model SW620 Colon adenocarcinoma Homo sapiens CVCL_0547
HT29 Colon cancer Mus musculus CVCL_A8EZ
HCT 8 Colon adenocarcinoma Homo sapiens CVCL_2478
In-vivo Model In vivo, the group of HCT116 cells labeled with luciferase were surgically injected into the spleen of nude mice. After 2 months, the nude mice were subjected to D-luciferin injection and the luciferase signals were monitored and quantified.
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary miR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor Krueppel-like factor 4 (KLF4). miR-1915-3p function as a tumor suppressor by targeting SET and has an anti-metastatic therapeutic potential for lung cancer treatment.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response TNF signaling pathway hsa04668
Cell Process Cell migration
Cell invasion
Epithelial-mesenchymal transition
In-vitro Model NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Experiment 2 Reporting the m6A-centered Disease Response [1]
Response Summary miR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor Krueppel-like factor 4 (KLF4). miR-1915-3p function as a tumor suppressor by targeting SET and has an anti-metastatic therapeutic potential for lung cancer treatment.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Down regulation
Pathway Response TNF signaling pathway hsa04668
Cell Process Cell migration
Cell invasion
Epithelial-mesenchymal transition
In-vitro Model NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Bladder cancer [ICD-11: 2C94]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary METTL3/YTHDF2/SETD7/Krueppel-like factor 4 (KLF4) m6 A axis provide the insight into the underlying mechanism of carcinogenesis and highlight potential therapeutic targets for bladder cancer.
Responsed Disease Bladder cancer [ICD-11: 2C94]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Cell Process Cancer proliferation
Cancer metastasis
In-vitro Model SV-HUC-1 Normal Homo sapiens CVCL_3798
T24 Bladder carcinoma Homo sapiens CVCL_0554
UM-UC-3 Bladder carcinoma Homo sapiens CVCL_1783
In-vivo Model For the subcutaneous implantation model, UM-UC-3 cells (2 × 106 cells per mouse) stably METTL3 knocked down (shMETTL3-1, shMETTL3-2) were injected into the flanks of mice.
Experiment 2 Reporting the m6A-centered Disease Response [2]
Response Summary METTL3/YTHDF2/SETD7/Krueppel-like factor 4 (KLF4) m6 A axis provide the insight into the underlying mechanism of carcinogenesis and highlight potential therapeutic targets for bladder cancer.
Responsed Disease Bladder cancer [ICD-11: 2C94]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Down regulation
Cell Process Cancer proliferation
Cancer metastasis
In-vitro Model SV-HUC-1 Normal Homo sapiens CVCL_3798
T24 Bladder carcinoma Homo sapiens CVCL_0554
UM-UC-3 Bladder carcinoma Homo sapiens CVCL_1783
In-vivo Model For the subcutaneous implantation model, UM-UC-3 cells (2 × 106 cells per mouse) stably METTL3 knocked down (shMETTL3-1, shMETTL3-2) were injected into the flanks of mice.
Atherosclerosis [ICD-11: BD40]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [4]
Response Summary In the in vivo atherosclerosis model,partial ligation of the carotid artery led to plaque formation and up-regulation of METTL3 and NLRP1, with down-regulation of KLF4; knockdown of METTL3 via repetitive shRNA administration prevented the atherogenic process, NLRP1 up-regulation, and Krueppel-like factor 4 (KLF4) down-regulation. Collectively, it has demonstrated that METTL3 serves a central role in the atherogenesis induced by oscillatory stress and disturbed blood flow.
Responsed Disease Atherosclerosis [ICD-11: BD40.Z]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
In-vitro Model MAEC Normal Mus musculus CVCL_U411
HUVEC-C Normal Homo sapiens CVCL_2959
References
Ref 1 MicroRNA-1915-3p inhibits cell migration and invasion by targeting SET in non-small-cell lung cancer. BMC Cancer. 2021 Nov 13;21(1):1218. doi: 10.1186/s12885-021-08961-8.
Ref 2 METTL3/YTHDF2 m(6) A axis promotes tumorigenesis by degrading SETD7 and KLF4 mRNAs in bladder cancer. J Cell Mol Med. 2020 Apr;24(7):4092-4104. doi: 10.1111/jcmm.15063. Epub 2020 Mar 3.
Ref 3 Methyl CpG binding protein 2 promotes colorectal cancer metastasis by regulating N(6) -methyladenosine methylation through methyltransferase-like 14. Cancer Sci. 2021 Aug;112(8):3243-3254. doi: 10.1111/cas.15011. Epub 2021 Jun 29.
Ref 4 METTL3-dependent N(6)-methyladenosine RNA modification mediates the atherogenic inflammatory cascades in vascular endothelium. Proc Natl Acad Sci U S A. 2021 Feb 16;118(7):e2025070118. doi: 10.1073/pnas.2025070118.