m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00274)
Target Name Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A)
Synonyms
HIF-1-alpha; HIF1-alpha; ARNT-interacting protein; Basic-helix-loop-helix-PAS protein MOP1; Class E basic helix-loop-helix protein 78; bHLHe78; Member of PAS protein 1; PAS domain-containing protein 8; BHLHE78; MOP1; PASD8
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Gene Name HIF1A
Chromosomal Location 14q23.2
Function
Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300. Activity is enhanced by interaction with NCOA1 and/or NCOA2. Interaction with redox regulatory protein APEX1 seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia. (Microbial infection) Upon infection by human coronavirus SARS-CoV-2, is required for induction of glycolysis in monocytes and the consequent proinflammatory state. In monocytes, induces expression of ACE2 and cytokines such as IL1B, TNF, IL6, and interferons. Promotes human coronavirus SARS-CoV-2 replication and monocyte inflammatory response.
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Gene ID 3091
Uniprot ID
HIF1A_HUMAN
HGNC ID
HGNC:4910
Ensembl Gene ID
ENSG00000100644
KEGG ID
hsa:3091
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
HIF1A 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 3 (METTL3) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line LX2 cell line Homo sapiens
Treatment: shMETTL3 LX2 cells
Control: shLuc LX2 cells
 GSE207909
Regulation
logFC: 1.13E+00
p-value: 4.17E-08
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 HBXIP drives metabolic reprogramming in hepatocellular carcinoma cells via METTL3-mediated m6A modification of Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A). Highly expressed HBXIP and METTL3 are associated with dismal oncologic outcomes of patients with hepatocellular carcinoma. The positive relation between HBXIP and METTL3 can activate reprogramming of HCC cell metabolism by inducing m6A modification of HIF-1-alpha, which is unraveled to enhance aggressive biological behaviors of HCC cells.
Target Regulation Up regulation
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Pathway Response HIF-1 signaling pathway hsa04066
Central carbon metabolism in cancer hsa05230
Cell Process Glycolysis
Glutaminolysis
In-vitro Model BEL-7402 Endocervical adenocarcinoma Homo sapiens CVCL_5492
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
L-02 Endocervical adenocarcinoma Homo sapiens CVCL_6926
MHCC97 Adult hepatocellular carcinoma Homo sapiens CVCL_4971
SMMC-7721 Endocervical adenocarcinoma Homo sapiens CVCL_0534
Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary IGF2BP3 positively regulated Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A) expression by directly binding to a specific m6A site in the coding region of HIF1A mRNA in gastric cancer cells. IGF2BP3 and HIF1A were highly expressed in GC tissues and hypoxia-treated GC cells.
Target Regulation Up regulation
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Cell Process Cell migration
In-vitro Model MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
HUVEC-C Normal Homo sapiens CVCL_2959
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
YTH domain-containing protein 2 (YTHDC2) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary YTHDC2 contributes to colon tumor metastasis by promoting translation of Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A) and that YTHDC2 is potentially a diagnostic marker and target gene for treating colon cancer patients.
Target Regulation Up regulation
Responsed Disease Colon cancer ICD-11: 2B90
 Disease Info 
Pathway Response HIF-1 signaling pathway hsa04066
Cell Process Biological regulation
In-vitro Model COS (From the African green monkey cell line (CV-1).)
HCT 116 Colon carcinoma Homo sapiens CVCL_0291
HT29 Colon cancer Mus musculus CVCL_A8EZ
In-vivo Model HCT116, Y2KD-116 and con-116 cells were resuspended at 1 × 106 cells per 50 ul of PBS. Cells were injected into the exteriorized spleen after abdominal incision.
Gastric cancer [ICD-11: 2B72]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary IGF2BP3 positively regulated Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A) expression by directly binding to a specific m6A site in the coding region of HIF1A mRNA in gastric cancer cells. IGF2BP3 and HIF1A were highly expressed in GC tissues and hypoxia-treated GC cells.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) READER
 Regulator Info 
Target Regulation Up regulation
Cell Process Cell migration
In-vitro Model MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
HUVEC-C Normal Homo sapiens CVCL_2959
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
Colon cancer [ICD-11: 2B90]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary YTHDC2 contributes to colon tumor metastasis by promoting translation of Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A) and that YTHDC2 is potentially a diagnostic marker and target gene for treating colon cancer patients.
Responsed Disease Colon cancer [ICD-11: 2B90]
Target Regulator YTH domain-containing protein 2 (YTHDC2) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response HIF-1 signaling pathway hsa04066
Cell Process Biological regulation
In-vitro Model COS (From the African green monkey cell line (CV-1).)
HCT 116 Colon carcinoma Homo sapiens CVCL_0291
HT29 Colon cancer Mus musculus CVCL_A8EZ
In-vivo Model HCT116, Y2KD-116 and con-116 cells were resuspended at 1 × 106 cells per 50 ul of PBS. Cells were injected into the exteriorized spleen after abdominal incision.
Liver cancer [ICD-11: 2C12]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary HBXIP drives metabolic reprogramming in hepatocellular carcinoma cells via METTL3-mediated m6A modification of Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A). Highly expressed HBXIP and METTL3 are associated with dismal oncologic outcomes of patients with hepatocellular carcinoma. The positive relation between HBXIP and METTL3 can activate reprogramming of HCC cell metabolism by inducing m6A modification of HIF-1-alpha, which is unraveled to enhance aggressive biological behaviors of HCC cells.
Responsed Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response HIF-1 signaling pathway hsa04066
Central carbon metabolism in cancer hsa05230
Cell Process Glycolysis
Glutaminolysis
In-vitro Model BEL-7402 Endocervical adenocarcinoma Homo sapiens CVCL_5492
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
L-02 Endocervical adenocarcinoma Homo sapiens CVCL_6926
MHCC97 Adult hepatocellular carcinoma Homo sapiens CVCL_4971
SMMC-7721 Endocervical adenocarcinoma Homo sapiens CVCL_0534
Inflammatory response [ICD-11: MG46]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response []
Response Summary lnc-Dpf3 directly bound to Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A) and suppressed HIF-1-alpha-dependent transcription of the glycolytic gene Ldha, thus inhibiting DC glycolytic metabolism and migratory capacity. CCR7-inducible lnc-Dpf3 in coupling epigenetic and metabolic pathways to feedback-control DC migration and inflammatory responses.
Responsed Disease Inflammatory response [ICD-11: MG46]
Pathway Response HIF-1 signaling pathway hsa04066
Cell Process Glycolysis
Immune responses
Inflammatory injuries
In-vitro Model ()
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In-vivo Model Positive ES cell clones were expanded and injected into C57BL/6J blastocysts to generate the chimeric offspring. The chimeric mice were mated with C57BL/6J mice to obtain the lnc-Dpf3 floxed heterozygous mouse (lnc-Dpf3fl/+). The lnc-Dpf3fl/+ mice were bred with C57BL/6J mice expressing the Cre recombinase under the control of the Itgax promoter (Itgax-cre mice; The Jackson Laboratory) to generate lnc-Dpf3 floxed heterozygous mouse with Itgax-cre allele (lnc-Dpf3fl/+Itgax-cre+). These mice were intercrossed to generate DC-specific lnc-Dpf3-deficient mice (lnc-Dpf3fl/flItgax-cre+) used for this study. Hif1afl/fl mice, a kindly gift from Dr. Ming Zhang (Renji Hospital, Medical College of Shanghai Jiaotong University, China) were crossed with Itgax-cre mice to generate DC-specific HIF-1-Alpha-deficient mice (Hif1afl/flItgax-cre+). All mice were maintained under specific pathogen-free conditions and used at 6-8 weeks of age.
References
Ref 1 HBXIP drives metabolic reprogramming in hepatocellular carcinoma cells via METTL3-mediated m6A modification of HIF-1Alpha. J Cell Physiol. 2021 May;236(5):3863-3880. doi: 10.1002/jcp.30128. Epub 2020 Dec 11.
Ref 2 Knockdown of m6A Reader IGF2BP3 Inhibited Hypoxia-Induced Cell Migration and Angiogenesis by Regulating Hypoxia Inducible Factor-1Alpha in Stomach Cancer. Front Oncol. 2021 Sep 21;11:711207. doi: 10.3389/fonc.2021.711207. eCollection 2021.
Ref 3 RNA helicase YTHDC2 promotes cancer metastasis via the enhancement of the efficiency by which HIF-1Alpha mRNA is translated. Cancer Lett. 2016 Jun 28;376(1):34-42. doi: 10.1016/j.canlet.2016.02.022. Epub 2016 Mar 17.