General Information of the m6A Target Gene (ID: M6ATAR00228)
Target Name Microprocessor complex subunit DGCR8 (DGCR8)
Synonyms
DiGeorge syndrome critical region 8; C22orf12; DGCRK6; LP4941
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Gene Name DGCR8
Chromosomal Location 22q11.21
Function
Component of the microprocessor complex that acts as a RNA- and heme-binding protein that is involved in the initial step of microRNA (miRNA) biogenesis. Component of the microprocessor complex that is required to process primary miRNA transcripts (pri-miRNAs) to release precursor miRNA (pre-miRNA) in the nucleus. Within the microprocessor complex, DGCR8 function as a molecular anchor necessary for the recognition of pri-miRNA at dsRNA-ssRNA junction and directs DROSHA to cleave 11 bp away form the junction to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic DICER to generate mature miRNAs. The heme-bound DGCR8 dimer binds pri-miRNAs as a cooperative trimer (of dimers) and is active in triggering pri-miRNA cleavage, whereas the heme-free DGCR8 monomer binds pri-miRNAs as a dimer and is much less active. Both double-stranded and single-stranded regions of a pri-miRNA are required for its binding. Specifically recognizes and binds N6-methyladenosine (m6A)-containing pri-miRNAs, a modification required for pri-miRNAs processing. Involved in the silencing of embryonic stem cell self-renewal (By similarity).
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Gene ID 54487
Uniprot ID
DGCR8_HUMAN
HGNC ID
HGNC:2847
Ensembl Gene ID
ENSG00000128191
KEGG ID
hsa:54487
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
DGCR8 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]
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: -9.09E-01
p-value: 2.99E-21
More Results Click to View More RNA-seq Results
In total 4 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary The m(6)A mark acts as a key post-transcriptional modification that promotes the initiation of miRNA biogenesis. METTL3 depletion reduced the binding of Microprocessor complex subunit DGCR8 (DGCR8) to pri-miRNAs and resulted in the global reduction of mature miRNAs and concomitant accumulation of unprocessed pri-miRNAs.
Target Regulation Up regulation
Cell Process miRNA maturation
MicroRNAs in cancer (hsa05206)
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
HUVEC-C Normal Homo sapiens CVCL_2959
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary METTL3 promoted cell proliferation, migration, invasion and tumorigenesis in PCa. METTL3 upregulating the level of m6A, and interacted with Microprocessor complex subunit DGCR8 (DGCR8) to recognize the m6A modification of pre-miR-182 to regulate its splicing and maturation and promote the high expression of miRNA.
Target Regulation UP regulation
Responsed Disease Prostate cancer ICD-11: 2C82
In-vitro Model WPMY-1 Normal Homo sapiens CVCL_3814
VCaP Prostate carcinoma Homo sapiens CVCL_2235
PC-3 Prostate carcinoma Homo sapiens CVCL_0035
LNCaP Prostate carcinoma Homo sapiens CVCL_0395
DU145 Prostate carcinoma Homo sapiens CVCL_0105
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary METTL3 could interact with Microprocessor complex subunit DGCR8 (DGCR8) protein and positively modulate pri-miR-320b maturation process in an N6-methyladenosine (m6A)-dependent manner. Therefore, our findings uncover a VEGF-C-independent mechanism of exosomal and intracellular miR-320b-mediated LN metastasis and identify miR-320b as a novel predictive marker and therapeutic target for LN metastasis in ESCC.
Target Regulation Up regulation
Responsed Disease Esophageal squamous cell carcinoma ICD-11: 2B70.1
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation
Cell migration
Cell invasion
Epithelial-mesenchymal transition
In-vitro Model TE-1 Esophageal squamous cell carcinoma Homo sapiens CVCL_1759
KYSE-30 Esophageal squamous cell carcinoma Homo sapiens CVCL_1351
KYSE-150 Esophageal squamous cell carcinoma Homo sapiens CVCL_1348
HET-1A Normal Homo sapiens CVCL_3702
CVCL_E307 Esophageal squamous cell carcinoma Homo sapiens CVCL_E307
Eca-109 Esophageal squamous cell carcinoma Homo sapiens CVCL_6898
In-vivo Model Luciferase-labeled KYSE150 cells (5 × 106) were inoculated into the footpads of BALB/c nude mice (4-5 weeks old, 18-20 g) to establish the popliteal lymphatic metastasis model.
Experiment 4 Reporting the m6A Methylation Regulator of This Target Gene [4]
Response Summary Interleukin 1-beta (IL-1-beta) is an important inducer of cartilage degeneration that can induce an inflammatory cascade reaction in chondrocytes and inhibit the normal biological function of cells. METTL3 could regulate miR-126-5p maturation, we first confirmed that METTL3 can bind the key protein underlying pri-miRNA processing, Microprocessor complex subunit DGCR8 (DGCR8). Additionally, when METTL3 expression was inhibited, the miR-126-5p maturation process was blocked.
Target Regulation Up regulation
Responsed Disease Chondropathies ICD-11: FB82
Cell Process RNA mature
In-vitro Model Cartilage cells (From the cartilage tissue samples from patients)
Methyltransferase-like 14 (METTL14) [WRITER]
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [5]
Response Summary METTL14 interacts with the microprocessor protein Microprocessor complex subunit DGCR8 (DGCR8) and positively modulates the primary microRNA 126 process in an m6 A-dependent manner. microRNA 126 inhibits the repressing effect of METTL14 in Hepatocellular carcinoma metastasis.
Target Regulation Up regulation
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
Cell Process Tumor metastasis
In-vitro Model HCC-1664 cell line (Primary HCC cells)
Hep 3B2.1-7 Childhood hepatocellular carcinoma Homo sapiens CVCL_0326
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
SMMC-7721 Endocervical adenocarcinoma Homo sapiens CVCL_0534
SMMC-7721 Endocervical adenocarcinoma Homo sapiens CVCL_0534
In-vivo Model Male athymic BALB/c nude mice (5 weeks old) were used. Subcutaneous tumor growth assays, liver metastasis model, and tail vein injection model were performed as described.Metastases were detected using the IVIS@Lumina II system (Caliper Life Sciences, Hopkinton, MA) 10 minutes after intraperitoneal injection of 4.0 mg luciferin (Gold Biotech) in 50 uL of saline.
Liver cancer [ICD-11: 2C12]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [5]
Response Summary METTL14 interacts with the microprocessor protein Microprocessor complex subunit DGCR8 (DGCR8) and positively modulates the primary microRNA 126 process in an m6 A-dependent manner. microRNA 126 inhibits the repressing effect of METTL14 in Hepatocellular carcinoma metastasis.
Responsed Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Up regulation
Cell Process Tumor metastasis
In-vitro Model HCC-1664 cell line (Primary HCC cells)
Hep 3B2.1-7 Childhood hepatocellular carcinoma Homo sapiens CVCL_0326
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
SMMC-7721 Endocervical adenocarcinoma Homo sapiens CVCL_0534
SMMC-7721 Endocervical adenocarcinoma Homo sapiens CVCL_0534
In-vivo Model Male athymic BALB/c nude mice (5 weeks old) were used. Subcutaneous tumor growth assays, liver metastasis model, and tail vein injection model were performed as described.Metastases were detected using the IVIS@Lumina II system (Caliper Life Sciences, Hopkinton, MA) 10 minutes after intraperitoneal injection of 4.0 mg luciferin (Gold Biotech) in 50 uL of saline.
Prostate cancer [ICD-11: 2C82]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary METTL3 promoted cell proliferation, migration, invasion and tumorigenesis in PCa. METTL3 upregulating the level of m6A, and interacted with Microprocessor complex subunit DGCR8 (DGCR8) to recognize the m6A modification of pre-miR-182 to regulate its splicing and maturation and promote the high expression of miRNA.
Responsed Disease Prostate cancer [ICD-11: 2C82]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation UP regulation
In-vitro Model WPMY-1 Normal Homo sapiens CVCL_3814
VCaP Prostate carcinoma Homo sapiens CVCL_2235
PC-3 Prostate carcinoma Homo sapiens CVCL_0035
LNCaP Prostate carcinoma Homo sapiens CVCL_0395
DU145 Prostate carcinoma Homo sapiens CVCL_0105
Oral cavity/oesophagus/stomach in situ carcinoma [ICD-11: 2E60]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary METTL3 could interact with Microprocessor complex subunit DGCR8 (DGCR8) protein and positively modulate pri-miR-320b maturation process in an N6-methyladenosine (m6A)-dependent manner. Therefore, our findings uncover a VEGF-C-independent mechanism of exosomal and intracellular miR-320b-mediated LN metastasis and identify miR-320b as a novel predictive marker and therapeutic target for LN metastasis in ESCC.
Responsed Disease Esophageal squamous cell carcinoma [ICD-11: 2B70.1]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation
Cell migration
Cell invasion
Epithelial-mesenchymal transition
In-vitro Model TE-1 Esophageal squamous cell carcinoma Homo sapiens CVCL_1759
KYSE-30 Esophageal squamous cell carcinoma Homo sapiens CVCL_1351
KYSE-150 Esophageal squamous cell carcinoma Homo sapiens CVCL_1348
HET-1A Normal Homo sapiens CVCL_3702
CVCL_E307 Esophageal squamous cell carcinoma Homo sapiens CVCL_E307
Eca-109 Esophageal squamous cell carcinoma Homo sapiens CVCL_6898
In-vivo Model Luciferase-labeled KYSE150 cells (5 × 106) were inoculated into the footpads of BALB/c nude mice (4-5 weeks old, 18-20 g) to establish the popliteal lymphatic metastasis model.
Chondropathies [ICD-11: FB82]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [4]
Response Summary Interleukin 1-beta (IL-1-beta) is an important inducer of cartilage degeneration that can induce an inflammatory cascade reaction in chondrocytes and inhibit the normal biological function of cells. METTL3 could regulate miR-126-5p maturation, we first confirmed that METTL3 can bind the key protein underlying pri-miRNA processing, Microprocessor complex subunit DGCR8 (DGCR8). Additionally, when METTL3 expression was inhibited, the miR-126-5p maturation process was blocked.
Responsed Disease Chondropathies [ICD-11: FB82]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Cell Process RNA mature
In-vitro Model Cartilage cells (From the cartilage tissue samples from patients)
References
Ref 1 N6-methyladenosine marks primary microRNAs for processing. Nature. 2015 Mar 26;519(7544):482-5. doi: 10.1038/nature14281. Epub 2015 Mar 18.
Ref 2 METTL3 promotes prostate cancer progression by regulating miR-182 maturation in m6A-dependent manner. Andrologia. 2022 Aug;54(7):1581-1591. doi: 10.1111/and.14422. Epub 2022 Apr 12.
Ref 3 Exosomal and intracellular miR-320b promotes lymphatic metastasis in esophageal squamous cell carcinoma. Mol Ther Oncolytics. 2021 Sep 25;23:163-180. doi: 10.1016/j.omto.2021.09.003. eCollection 2021 Dec 17.
Ref 4 METTL3 promotes IL-1Beta-induced degeneration of endplate chondrocytes by driving m6A-dependent maturation of miR-126-5p. J Cell Mol Med. 2020 Dec;24(23):14013-14025. doi: 10.1111/jcmm.16012. Epub 2020 Oct 23.
Ref 5 METTL14 suppresses the metastatic potential of hepatocellular carcinoma by modulating N(6) -methyladenosine-dependent primary MicroRNA processing. Hepatology. 2017 Feb;65(2):529-543. doi: 10.1002/hep.28885. Epub 2016 Dec 24.