m6A-centered Disease Response Information
General Information of the Disease (ID: M6ADIS0001)
Name |
Brain cancer
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ICD |
ICD-11: 2A00
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Full List of Target Gene(s) of This m6A-centered Disease Response
Beta-catenin-interacting protein 1 (CTNNBIP1)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [1] | |||
Response Summary | METTL3-mediated m6A modification upregulated circDLC1 expression, and circDLC1 promoted Beta-catenin-interacting protein 1 (CTNNBIP1) transcription by sponging miR-671-5p, thus repressing the malignant proliferation of glioma. | |||
Responsed Disease | Glioma [ICD-11: 2A00.0] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Up regulation | |||
In-vitro Model | T98G | Glioblastoma | Homo sapiens | CVCL_0556 |
LN-229 | Glioblastoma | Homo sapiens | CVCL_0393 | |
LN-18 | Glioblastoma | Homo sapiens | CVCL_0392 | |
HEB (human normal glial cell line HEB were obtained from Tongpai (Shanghai) biotechnology co., LTD (Shanghai, China)) | ||||
A-172 | Glioblastoma | Homo sapiens | CVCL_0131 | |
CCAAT/enhancer-binding protein alpha (CEBPA)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [2] | |||
Response Summary | This work demonstrates anti-tumor effects of 2HG in inhibiting proliferation/survival of FTO-high cancer cells via targeting FTO/m6A/MYC/CCAAT/enhancer-binding protein alpha (CEBPA) signaling.High levels of FTO sensitize leukemia cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling. R-2HG also displays anti-tumor activity in glioma. High levels of FTO sensitize leukemic cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling. | |||
Responsed Disease | Glioma [ICD-11: 2A00.0] | |||
Responsed Drug | R-2HG | Investigative | ||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
Target Regulation | Down regulation | |||
Cell Process | Glutamine metabolism | |||
Cell apoptosis | ||||
In-vitro Model | 8-MG-BA | Glioblastoma | Homo sapiens | CVCL_1052 |
A-172 | Glioblastoma | Homo sapiens | CVCL_0131 | |
DK-MG | Glioblastoma | Homo sapiens | CVCL_1173 | |
GaMG | Glioblastoma | Homo sapiens | CVCL_1226 | |
HEL | Erythroleukemia | Homo sapiens | CVCL_0001 | |
Jurkat | T acute lymphoblastic leukemia | Homo sapiens | CVCL_0065 | |
KOCL-45 | B acute lymphoblastic leukemia | Homo sapiens | CVCL_3993 | |
KOCL-48 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_6867 | |
KOCL-50 | B acute lymphoblastic leukemia | Homo sapiens | CVCL_6866 | |
KOCL-51 | B acute lymphoblastic leukemia | Homo sapiens | CVCL_6865 | |
KOCL-69 | B acute lymphoblastic leukemia | Homo sapiens | CVCL_3995 | |
KOPN-1 | B acute lymphoblastic leukemia | Homo sapiens | CVCL_3937 | |
LN-18 | Glioblastoma | Homo sapiens | CVCL_0392 | |
LN-229 | Glioblastoma | Homo sapiens | CVCL_0393 | |
MA9.3 (MA9.3) | ||||
MA9.6ITD (MLL-AF9 plus FLT3-ITD) | ||||
MA9.6RAS (MLL-AF9 plus NRasG12D) | ||||
MA9.6 (MLL-AF9) | ||||
MA9.6ITD (MLL-AF9 plus FLT3-ITD) | ||||
MA9.6RAS (MLL-AF9 plus NRasG12D) | ||||
ME-1 [Human leukemia] | Adult acute myeloid leukemia | Homo sapiens | CVCL_2110 | |
ML-2 | Adult acute myeloid leukemia | Homo sapiens | CVCL_1418 | |
MV4-11 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 | |
NB4 | Acute promyelocytic leukemia | Homo sapiens | CVCL_0005 | |
NOMO-1 | Adult acute monocytic leukemia | Homo sapiens | CVCL_1609 | |
PL21 | Familial adenomatous polyposis | Homo sapiens | CVCL_JM48 | |
T98G | Glioblastoma | Homo sapiens | CVCL_0556 | |
THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 | |
U-937 | Adult acute monocytic leukemia | Homo sapiens | CVCL_0007 | |
In-vivo Model | For R-2HG injection mouse models, sensitive (NOMO-1 and MA9.3ITD) or resistant (MA9.3RAS) cells were injected into NSGS or NRGS intravenously, and then R-2HG (6mg/kg body weight) or PBS were injected once daily through tail vein for 12 consecutive days starting from day 11 post xeno-transplantation. | |||
CD44 antigen (CD44)
In total 2 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [3] | |||
Response Summary | HNRNPA2B1 and HNRNPC were extensively expressed in the Glioblastoma multiforme(GBM) microenvironment.m6A regulators promoted the stemness state in GBM cancer cells. Cell communication analysis identified genes in the GALECTIN signaling network in GBM samples, and expression of these genes (LGALS9, CD44 antigen (CD44), CD45, and HAVCR2) correlated with that of m6A regulators. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) | READER | ||
In-vitro Model | U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 |
THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene | [3] | |||
Response Summary | HNRNPA2B1 and HNRNPC were extensively expressed in the Glioblastoma multiforme(GBM) microenvironment. m6A regulators promoted the stemness state in GBM cancer cells. Cell communication analysis identified genes in the GALECTIN signaling network in GBM samples, and expression of these genes (LGALS9, CD44 antigen (CD44), CD45, and HAVCR2) correlated with that of m6A regulators. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC) | READER | ||
In-vitro Model | U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 |
THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
Cystine/glutamate transporter (SLC7A11)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [4] | |||
Response Summary | This study NKAP knockdown induced cell death in glioblastoma cells. NKAP acted as a new ferroptosis suppressor by binding to m6A and then promoting Cystine/glutamate transporter (SLC7A11) mRNA splicing and maturation. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | NF-kappa-B-activating protein (NKAP) | READER | ||
Target Regulation | Up regulation | |||
Pathway Response | Ferroptosis | hsa04216 | ||
Cell Process | Ferroptosis | |||
In-vitro Model | U87MG (Astroblastoma cells from human brain) | |||
U251 (Fibroblasts or fibroblast like cells) | ||||
In-vivo Model | The male BALB/c nude mice were randomized divide into two groups, each group including six 4 weeks old nude mice. Investigators were blinded to the treatment groups during data collection and subsequent data analysis. In the subcutaneous xenograft model, 5 × 105 cells were subcutaneously injected in the right flanks of nude mice. In the orthotopic intracranial mouse model, each mouse was intracranially injected with 1 × 105 luciferase transfected U87MG cells in 10 uL PBS solution. | |||
DNA-3-methyladenine glycosylase (ANPG/MPG)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [5] | |||
Response Summary | Two critical DNA repair genes (MGMT and DNA-3-methyladenine glycosylase (ANPG/MPG)) were m6A-modified by METTL3, whereas inhibited by METTL3 silencing or DAA-mediated total methylation inhibition, which is crucial for METTL3-improved temozolomide resistance in glioblastoma cells. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Responsed Drug | Temozolomide | Approved | ||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Down regulation | |||
Pathway Response | Nucleotide excision repair | hsa03420 | ||
Cell Process | DNA repair | |||
In-vitro Model | U251 (Fibroblasts or fibroblast like cells) | |||
U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 | |
In-vivo Model | Subcutaneously injected shMETTL3 or shNC-expressing U87-MG-TMZ cells into BALB/c NOD mice. After confirmation of GBM implantation, mice were treated with TMZ (66 mg/kg/d, 5 d per week, for 3 cycles). | |||
Ephrin type-B receptor 3 (EPHB3)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [6] | |||
Response Summary | YTHDF2 enhanced TMZ resistance in GBM by activation of the PI3K/Akt and NF-Kappa-B signalling pathways via inhibition of Ephrin type-B receptor 3 (EPHB3) and TNFAIP3. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Responsed Drug | Temozolomide | Approved | ||
Target Regulator | YTH domain-containing family protein 2 (YTHDF2) | READER | ||
Target Regulation | Down regulation | |||
Pathway Response | PI3K-Akt signaling pathway | hsa04151 | ||
Cell Process | RNA stability | |||
In-vitro Model | T98G | Glioblastoma | Homo sapiens | CVCL_0556 |
LN-229 | Glioblastoma | Homo sapiens | CVCL_0393 | |
In-vivo Model | 5 × 106 infected T98G cells (LV-NC or LV-YTHDF2) were injected into the flanks of mice through subcutaneous. | |||
Forkhead box protein M1 (FOXM1)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [7] | |||
Response Summary | ALKBH5 and FOXM1-AS disrupted GSC tumorigenesis through the Forkhead box protein M1 (FOXM1) axis. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | RNA demethylase ALKBH5 (ALKBH5) | ERASER | ||
Target Regulation | Up regulation | |||
Pathway Response | Glioma | hsa05214 | ||
Cell Process | Cells proliferation | |||
Signaling pathways regulating pluripotency of stem cells (hsa04550) | ||||
In-vitro Model | LN-229 | Glioblastoma | Homo sapiens | CVCL_0393 |
Hs 683 | Oligodendroglioma | Homo sapiens | CVCL_0844 | |
SW1783 | Anaplastic astrocytoma | Homo sapiens | CVCL_1722 | |
U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 | |
In-vivo Model | For the animal survival analysis, mice were intracranially injected with 10,000 GSCs and maintained until moribund or 80 days after injection. For the rescue studies, GSCs with ALKBH5 or FOXM1-AS shRNAs were co-transfected with a FOXM1, ALKBH5 wild-type or mutant expression construct. | |||
Galectin-9 (LGALS9)
In total 2 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [3] | |||
Response Summary | HNRNPA2B1 and HNRNPC were extensively expressed in the Glioblastoma multiforme(GBM) microenvironment.m6A regulators promoted the stemness state in GBM cancer cells. Cell communication analysis identified genes in the GALECTIN signaling network in GBM samples, and expression of these genes (Galectin-9 (LGALS9), CD44, CD45, and HAVCR2) correlated with that of m6A regulators. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) | READER | ||
In-vitro Model | U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 |
THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene | [3] | |||
Response Summary | HNRNPA2B1 and HNRNPC were extensively expressed in the Glioblastoma multiforme(GBM) microenvironment. m6A regulators promoted the stemness state in GBM cancer cells. Cell communication analysis identified genes in the GALECTIN signaling network in GBM samples, and expression of these genes (Galectin-9 (LGALS9), CD44, CD45, and HAVCR2) correlated with that of m6A regulators. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC) | READER | ||
In-vitro Model | U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 |
THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
Heat shock protein HSP 90-alpha (HSP90/HSP90AA1)
In total 2 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [8] | |||
Response Summary | m6A regulated cell proliferation by influencing apoptosis of U251 cells through regulating Heat shock protein HSP 90-alpha (HSP90/HSP90AA1) expression. m6A level was decreased in glioma tissue, which was caused by decreased METTL3 and increased FTO levels. | |||
Responsed Disease | Glioma [ICD-11: 2A00.0] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Down regulation | |||
Cell Process | Cell migration and proliferation | |||
In-vitro Model | U251 (Fibroblasts or fibroblast like cells) | |||
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene | [8] | |||
Response Summary | m6A regulated cell proliferation by influencing apoptosis of U251 cells through regulating Heat shock protein HSP 90-alpha (HSP90/HSP90AA1) expression.m6A level was decreased in glioma tissue, which was caused by decreased METTL3 and increased FTO levels. | |||
Responsed Disease | Glioma [ICD-11: 2A00.0] | |||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
Target Regulation | Down regulation | |||
Cell Process | Cell migration and proliferation | |||
In-vitro Model | U251 (Fibroblasts or fibroblast like cells) | |||
Hepatitis A virus cellular receptor 2 (HAVCR2)
In total 2 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [3] | |||
Response Summary | HNRNPA2B1 and HNRNPC were extensively expressed in the Glioblastoma multiforme(GBM) microenvironment.m6A regulators promoted the stemness state in GBM cancer cells. Cell communication analysis identified genes in the GALECTIN signaling network in GBM samples, and expression of these genes (LGALS9, CD44, CD45, and Hepatitis A virus cellular receptor 2 (HAVCR2)) correlated with that of m6A regulators. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) | READER | ||
In-vitro Model | U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 |
THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene | [3] | |||
Response Summary | HNRNPA2B1 and HNRNPC were extensively expressed in the Glioblastoma multiforme(GBM) microenvironment. m6A regulators promoted the stemness state in GBM cancer cells. Cell communication analysis identified genes in the GALECTIN signaling network in GBM samples, and expression of these genes (LGALS9, CD44, CD45, and Hepatitis A virus cellular receptor 2 (HAVCR2)) correlated with that of m6A regulators. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC) | READER | ||
In-vitro Model | U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 |
THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
Homeobox protein NANOG (NANOG)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [9] | |||
Response Summary | In glioma, hsa_circ_0072083 could regulate Homeobox protein NANOG (NANOG) and ALKBH5 via targeting miR-1252-5p to control temozolomide resistance. circ_0072083 silence reduced NANOG expression via blocking ALKBH5-mediated demethylation. | |||
Responsed Disease | Glioma [ICD-11: 2A00.0] | |||
Responsed Drug | Temozolomide | Approved | ||
Target Regulator | RNA demethylase ALKBH5 (ALKBH5) | ERASER | ||
Target Regulation | Up regulation | |||
Cell Process | Cellular Processes | |||
Cell growth and death | ||||
Cell apoptosis | ||||
In-vitro Model | HEK293T | Normal | Homo sapiens | CVCL_0063 |
U251 (Fibroblasts or fibroblast like cells) | ||||
U87 (A primary glioblastoma cell line) | ||||
In-vivo Model | U251/TR cells (2 × 106 per mouse) with stable transfection of sh-circ_0072083 or sh-NC were subcutaneously injected into mice. | |||
Interferon-inducible protein 4 (ADAR1)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [10] | |||
Response Summary | METTL3, upregulated in glioblastoma, methylates Interferon-inducible protein 4 (ADAR1) mRNA and increases its protein level leading to a pro-tumorigenic mechanism connecting METTL3, YTHDF1, and ADAR1. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Up regulation | |||
Pathway Response | mRNA surveillance pathway | hsa03015 | ||
RNA degradation | hsa03018 | |||
Cell Process | RNA stability | |||
In-vitro Model | U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 |
U-118MG | Astrocytoma | Homo sapiens | CVCL_0633 | |
T98G | Glioblastoma | Homo sapiens | CVCL_0556 | |
A-172 | Glioblastoma | Homo sapiens | CVCL_0131 | |
In-vivo Model | 2 × 106 U87MG cells already expressing shscr or shADAR1 were subcutaneously injected in the flank of 6-week-old nude mice (nu/nu, Charles River, Wilmington, MA, USA). | |||
Interleukin enhancer-binding factor 3 (ILF3)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [11] | |||
Response Summary | loss of m6A RNA methylation and increased translation in human glioblastoma cells as well as a role for miRNAs in the modulation of m6A RNA demethylation in genes that are most efficiently translated during glioma stem cells differentiation. Ectopic expression of the RRACH-binding miR-145 induces loss of m6A, formation of FTO/AGO1/Interleukin enhancer-binding factor 3 (ILF3)/miR-145 complexes on a clinically relevant tumor suppressor gene (CLIP3) and significant increase in its nascent translation. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
Target Regulation | Up regulation | |||
In-vitro Model | GBM1 | Glioblastoma | Homo sapiens | CVCL_DG57 |
GBM2 | Glioblastoma | Homo sapiens | CVCL_DG58 | |
GBM3 | Glioblastoma | Homo sapiens | CVCL_DG59 | |
Meltrin-beta (ADAM19)
In total 2 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [12] | |||
Response Summary | Knockdown of METTL3 or METTL14 induced changes in mRNA m6A enrichment and altered mRNA expression of genes (e.g., Meltrin-beta (ADAM19)) with critical biological functions in GSCs. Treatment with MA2, a chemical inhibitor of FTO, dramatically suppressed GSC-induced tumorigenesis and prolonged lifespan in GSC-grafted animals. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Down regulation | |||
Cell Process | Cells growth | |||
Cells self-renewal | ||||
Tumorigenesis | ||||
MicroRNAs in cancer (hsa05206) | ||||
In-vitro Model | GSC | Glioma | Epinephelus akaara | CVCL_M752 |
In-vivo Model | 2 × 105 dissociated cells in 2 uL PBS were injected into the following site (anteroposterior [AP] +0.6 mm, mediolateral [ML] +1.6 mm, and dorsoventricular [DV] 2.6 mm) with a rate of 1 uL/min. | |||
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene | [12] | |||
Response Summary | Knockdown of METTL3 or METTL14 induced changes in mRNA m6A enrichment and altered mRNA expression of genes (e.g., Meltrin-beta (ADAM19)) with critical biological functions in GSCs. Treatment with MA2, a chemical inhibitor of FTO, dramatically suppressed GSC-induced tumorigenesis and prolonged lifespan in GSC-grafted animals. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | Methyltransferase-like 14 (METTL14) | WRITER | ||
Target Regulation | Down regulation | |||
Cell Process | Cells growth | |||
Cells self-renewal | ||||
Tumorigenesis | ||||
MicroRNAs in cancer (hsa05206) | ||||
In-vitro Model | GSC | Glioma | Epinephelus akaara | CVCL_M752 |
In-vivo Model | 2 × 105 dissociated cells in 2 uL PBS were injected into the following site (anteroposterior [AP] +0.6 mm, mediolateral [ML] +1.6 mm, and dorsoventricular [DV] 2.6 mm) with a rate of 1 uL/min. | |||
Methylated-DNA--protein-cysteine methyltransferase (MGMT)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [5] | |||
Response Summary | Two critical DNA repair genes (Methylated-DNA--protein-cysteine methyltransferase (MGMT) and APNG) were m6A-modified by METTL3, whereas inhibited by METTL3 silencing or DAA-mediated total methylation inhibition, which is crucial for METTL3-improved temozolomide resistance in glioblastoma cells. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Responsed Drug | Temozolomide | Approved | ||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Down regulation | |||
Pathway Response | Nucleotide excision repair | hsa03420 | ||
Cell Process | DNA repair | |||
In-vitro Model | U251 (Fibroblasts or fibroblast like cells) | |||
U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 | |
In-vivo Model | Subcutaneously injected shMETTL3 or shNC-expressing U87-MG-TMZ cells into BALB/c NOD mice. After confirmation of GBM implantation, mice were treated with TMZ (66 mg/kg/d, 5 d per week, for 3 cycles). | |||
Myc proto-oncogene protein (MYC)
In total 5 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [13] | |||
Response Summary | The IGF1/IGF1R inhibitor, linsitinib for further investigation based upon the role of the IGF pathway member, IGFBP3, as a downstream effector of YTHDF2-Myc proto-oncogene protein (MYC) axis in GSCs. Inhibiting glioblastoma stem cells viability without affecting NSCs and impairing in vivo glioblastoma growth. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Responsed Drug | Linsitinib | Phase 3 | ||
Target Regulator | YTH domain-containing family protein 2 (YTHDF2) | READER | ||
Target Regulation | Up regulation | |||
In-vitro Model | NSC11 (Pluripotent derived neural progenitor cell) | |||
NHA (Normal human astrocytes) | ||||
HNP1 (A human neural progenitor cell) | ||||
ENSA (A human embryonic stem derived neural progenitor cell) | ||||
In-vivo Model | Implanting 5000 human derived GSCs into the right cerebral cortex of NSG mice at a depth of 3.5 mm under a University of California, San Diego Institutional Animal Care and Use Committee (IACUC) approved protocol. Brains were harvested and fixed in 4% formaldehyde, cryopreserved in 30% sucrose, and then cryosectioned. Hematoxylin and eosin (H&E) staining was performed on sections for histological analysis. In parallel survival experiments, mice were observed until the development of neurological signs. For in vivo drug treatment studies, intracranial xenografts were generated by implanting 5000 patient-derived GSCs (387 and 4121) into the right cerebral cortex of NSG mice as described above. Mice recovered for 7 days were randomly assigned into drug vs. treatment group by a blinded investigator. Mice were then treated daily with either vehicle (25 mM Tartaric acid) or 50 mg/kg linsitinib by oral gavage. | |||
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene | [2] | |||
Response Summary | This work demonstrates anti-tumor effects of 2HG in inhibiting proliferation/survival of FTO-high cancer cells via targeting FTO/m6A/Myc proto-oncogene protein (MYC)/CEBPA signaling.High levels of FTO sensitize leukemia cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling. R-2HG also displays anti-tumor activity in glioma. High levels of FTO sensitize leukemic cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling. | |||
Responsed Disease | Glioma [ICD-11: 2A00.0] | |||
Responsed Drug | R-2HG | Investigative | ||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
Target Regulation | Down regulation | |||
Cell Process | Glutamine metabolism | |||
Cell apoptosis | ||||
In-vitro Model | 8-MG-BA | Glioblastoma | Homo sapiens | CVCL_1052 |
A-172 | Glioblastoma | Homo sapiens | CVCL_0131 | |
DK-MG | Glioblastoma | Homo sapiens | CVCL_1173 | |
GaMG | Glioblastoma | Homo sapiens | CVCL_1226 | |
HEL | Erythroleukemia | Homo sapiens | CVCL_0001 | |
Jurkat | T acute lymphoblastic leukemia | Homo sapiens | CVCL_0065 | |
KOCL-45 | B acute lymphoblastic leukemia | Homo sapiens | CVCL_3993 | |
KOCL-48 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_6867 | |
KOCL-50 | B acute lymphoblastic leukemia | Homo sapiens | CVCL_6866 | |
KOCL-51 | B acute lymphoblastic leukemia | Homo sapiens | CVCL_6865 | |
KOCL-69 | B acute lymphoblastic leukemia | Homo sapiens | CVCL_3995 | |
KOPN-1 | B acute lymphoblastic leukemia | Homo sapiens | CVCL_3937 | |
LN-18 | Glioblastoma | Homo sapiens | CVCL_0392 | |
LN-229 | Glioblastoma | Homo sapiens | CVCL_0393 | |
MA9.3 (MA9.3) | ||||
MA9.6ITD (MLL-AF9 plus FLT3-ITD) | ||||
MA9.6RAS (MLL-AF9 plus NRasG12D) | ||||
MA9.6 (MLL-AF9) | ||||
MA9.6ITD (MLL-AF9 plus FLT3-ITD) | ||||
MA9.6RAS (MLL-AF9 plus NRasG12D) | ||||
ME-1 [Human leukemia] | Adult acute myeloid leukemia | Homo sapiens | CVCL_2110 | |
ML-2 | Adult acute myeloid leukemia | Homo sapiens | CVCL_1418 | |
MV4-11 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 | |
NB4 | Acute promyelocytic leukemia | Homo sapiens | CVCL_0005 | |
NOMO-1 | Adult acute monocytic leukemia | Homo sapiens | CVCL_1609 | |
PL21 | Familial adenomatous polyposis | Homo sapiens | CVCL_JM48 | |
T98G | Glioblastoma | Homo sapiens | CVCL_0556 | |
THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 | |
U-937 | Adult acute monocytic leukemia | Homo sapiens | CVCL_0007 | |
In-vivo Model | For R-2HG injection mouse models, sensitive (NOMO-1 and MA9.3ITD) or resistant (MA9.3RAS) cells were injected into NSGS or NRGS intravenously, and then R-2HG (6mg/kg body weight) or PBS were injected once daily through tail vein for 12 consecutive days starting from day 11 post xeno-transplantation. | |||
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene | [13] | |||
Response Summary | YTHDF2 depletion downregulated IGFBP3 mRNA and protein levels, without affecting its mRNA stability. YTHDF2 regulated IGFBP3 levels via Myc proto-oncogene protein (MYC) in glioblastoma stem cells. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | Insulin-like growth factor-binding protein 3 (IGFBP3) | READER | ||
In-vitro Model | ENSA (A human embryonic stem derived neural progenitor cell) | |||
HNP1 (A human neural progenitor cell) | ||||
NSC11 (Pluripotent derived neural progenitor cell) | ||||
NHA (Normal human astrocytes) | ||||
In-vivo Model | Implanting 5000 human derived GSCs into the right cerebral cortex of NSG mice at a depth of 3.5 mm under a University of California, San Diego Institutional Animal Care and Use Committee (IACUC) approved protocol. Brains were harvested and fixed in 4% formaldehyde, cryopreserved in 30% sucrose, and then cryosectioned. Hematoxylin and eosin (H&E) staining was performed on sections for histological analysis. In parallel survival experiments, mice were observed until the development of neurological signs. For in vivo drug treatment studies, intracranial xenografts were generated by implanting 5000 patient-derived GSCs (387 and 4121) into the right cerebral cortex of NSG mice as described above. Mice recovered for 7 days were randomly assigned into drug vs. treatment group by a blinded investigator. Mice were then treated daily with either vehicle (25 mM Tartaric acid) or 50 mg/kg linsitinib by oral gavage. | |||
Experiment 4 Reporting the m6A-centered Disease Response by This Target Gene | [13] | |||
Response Summary | The m6A reader YTHDF2 stabilized Myc proto-oncogene protein (MYC) mRNA specifically in cancer stem cells. Given the challenge of targeting MYC, YTHDF2 presents a therapeutic target to perturb MYC signaling in glioblastoma. The IGF1/IGF1R inhibitor linsitinib preferentially targeted YTHDF2-expressing cells, inhibiting GSC viability without affecting NSCs and impairing in vivo glioblastoma growth. YTHDF2 links RNA epitranscriptomic modifications and GSC growth, laying the foundation for the YTHDF2-MYC-IGFBP3 axis as a specific and novel therapeutic target in glioblastoma. | |||
Responsed Disease | Glioma [ICD-11: 2A00.0] | |||
Target Regulator | YTH domain-containing family protein 2 (YTHDF2) | READER | ||
Target Regulation | Up regulation | |||
Pathway Response | RNA degradation | hsa03018 | ||
Cell Process | RNA stability | |||
In-vitro Model | () | |||
HNP1 (A human neural progenitor cell) | ||||
NHA (Normal human astrocytes) | ||||
NSC11 (Pluripotent derived neural progenitor cell) | ||||
In-vivo Model | For in vivo drug treatment studies, intracranial xenografts were generated by implanting 5000 patient-derived GSCs (387 and 4121) into the right cerebral cortex of NSG mice as described above. | |||
Experiment 5 Reporting the m6A-centered Disease Response by This Target Gene | [13] | |||
Response Summary | The m6A reader YTHDF2 stabilized Myc proto-oncogene protein (MYC) mRNA specifically in cancer stem cells. Given the challenge of targeting MYC, YTHDF2 presents a therapeutic target to perturb MYC signaling in glioblastoma. The IGF1/IGF1R inhibitor linsitinib preferentially targeted YTHDF2-expressing cells, inhibiting GSC viability without affecting NSCs and impairing in vivo glioblastoma growth. YTHDF2 links RNA epitranscriptomic modifications and GSC growth, laying the foundation for the YTHDF2-MYC-IGFBP3 axis as a specific and novel therapeutic target in glioblastoma. | |||
Responsed Disease | Glioma [ICD-11: 2A00.0] | |||
Target Regulator | Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) | READER | ||
Target Regulation | Up regulation | |||
Pathway Response | RNA degradation | hsa03018 | ||
Cell Process | RNA stability | |||
In-vitro Model | () | |||
HNP1 (A human neural progenitor cell) | ||||
NHA (Normal human astrocytes) | ||||
NSC11 (Pluripotent derived neural progenitor cell) | ||||
In-vivo Model | For in vivo drug treatment studies, intracranial xenografts were generated by implanting 5000 patient-derived GSCs (387 and 4121) into the right cerebral cortex of NSG mice as described above. | |||
Nuclear factor NF-kappa-B p105 subunit (NF-Kappa-B/NFKB1)
In total 2 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [14] | |||
Response Summary | YTHDF2 accelerated UBXN1 mRNA degradation via METTL3-mediated m6A, which, in turn, promoted Nuclear factor NF-kappa-B p105 subunit (NF-Kappa-B/NFKB1) activation. YTHDF2 promotes the malignant progression of gliomas and revealed important insight into the upstream regulatory mechanism of NF-Kappa-B activation via UBXN1 with a primary focus on m6A modification. | |||
Responsed Disease | Glioma [ICD-11: 2A00.0] | |||
Target Regulator | YTH domain-containing family protein 2 (YTHDF2) | READER | ||
Target Regulation | Up regulation | |||
Pathway Response | NF-kappa B signaling pathway | hsa04064 | ||
In-vitro Model | U87 (A primary glioblastoma cell line) | |||
N33 (The GBM patient-derived cell line) | ||||
LN-229 | Glioblastoma | Homo sapiens | CVCL_0393 | |
H4 | Astrocytoma | Homo sapiens | CVCL_1239 | |
In-vivo Model | Five-week-old female BALB/c nude mice (Charles Rivers, Beijing, China) were selected for the experiments. U87 cells (5 × 105) transfected with an empty vector, YTHDF2 overexpression, or METTL3 overexpression vectors were suspended in PBS and injected into the right frontal node of nude mice. The inoculation position was 2 mm lateral and 2 mm posterior to the anterior fontanel. Tumor size was estimated from luciferase volume measurements and MRI. The mice were sacrificed when they exhibited disturbed activity or convulsion. The brain was then harvested and embedded in paraffin. | |||
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene | [14] | |||
Response Summary | YTHDF2 accelerated UBXN1 mRNA degradation via METTL3-mediated m6A, which, in turn, promoted Nuclear factor NF-kappa-B p105 subunit (NF-Kappa-B/NFKB1) activation. YTHDF2 promotes the malignant progression of gliomas and revealed important insight into the upstream regulatory mechanism of NF-Kappa-B activation via UBXN1 with a primary focus on m6A modification. | |||
Responsed Disease | Glioma [ICD-11: 2A00.0] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Up regulation | |||
Pathway Response | NF-kappa B signaling pathway | hsa04064 | ||
In-vitro Model | U87 (A primary glioblastoma cell line) | |||
N33 (The GBM patient-derived cell line) | ||||
LN-229 | Glioblastoma | Homo sapiens | CVCL_0393 | |
H4 | Astrocytoma | Homo sapiens | CVCL_1239 | |
In-vivo Model | Five-week-old female BALB/c nude mice (Charles Rivers, Beijing, China) were selected for the experiments. U87 cells (5 × 105) transfected with an empty vector, YTHDF2 overexpression, or METTL3 overexpression vectors were suspended in PBS and injected into the right frontal node of nude mice. The inoculation position was 2 mm lateral and 2 mm posterior to the anterior fontanel. Tumor size was estimated from luciferase volume measurements and MRI. The mice were sacrificed when they exhibited disturbed activity or convulsion. The brain was then harvested and embedded in paraffin. | |||
Oxysterols receptor LXR-alpha (LXRA)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [15] | |||
Response Summary | YTHDF2 facilitates m6A-dependent mRNA decay of Oxysterols receptor LXR-alpha (LXRA) and HIVEP2, which impacts the glioma patient survival. YTHDF2 promotes tumorigenesis of GBM cells, largely through the downregulation of LXRA and HIVEP2. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | YTH domain-containing family protein 2 (YTHDF2) | READER | ||
Target Regulation | Down regulation | |||
Pathway Response | mRNA surveillance pathway | hsa03015), RNA degradation | ||
Cell Process | RNA stability | |||
In-vitro Model | U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 |
U-251MG | Astrocytoma | Homo sapiens | CVCL_0021 | |
T98G | Glioblastoma | Homo sapiens | CVCL_0556 | |
SW1783 | Anaplastic astrocytoma | Homo sapiens | CVCL_1722 | |
LN-229 | Glioblastoma | Homo sapiens | CVCL_0393 | |
Hs 683 | Oligodendroglioma | Homo sapiens | CVCL_0844 | |
GSC7-2 (GSC7-2 were obtained from fresh surgical specimens of human primary and recurrent glioma) | ||||
GSC6-27 (GSC6-27 were obtained from fresh surgical specimens of human primary and recurrent glioma) | ||||
GSC23 | Glioblastoma | Homo sapiens | CVCL_DR59 | |
GSC20 (GSC20 were obtained from fresh surgical specimens of human primary and recurrent glioma) | ||||
GSC17 | Glioblastoma | Homo sapiens | CVCL_DR57 | |
GSC11 | Glioblastoma | Homo sapiens | CVCL_DR55 | |
In-vivo Model | For the studies of investigating mice survival, mice were intracranially injected with 10,000 GSC11, 10,000 GSC7-2, or 500,000 LN229 cells. | |||
PDH kinase 1 (PDK1)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [16] | |||
Response Summary | Long noncoding RNA just proximal to X-inactive specific transcript facilitates aerobic glycolysis and temozolomide chemoresistance by promoting stability of PDH kinase 1 (PDK1) mRNA in an m6A-dependent manner in glioblastoma multiforme cells. JPX interacted with N6-methyladenosine (m6A) demethylase FTO alpha-ketoglutarate dependent dioxygenase (FTO) and enhanced FTO-mediated PDK1 mRNA demethylation. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Responsed Drug | Temozolomide | Approved | ||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
Target Regulation | Up regulation | |||
Pathway Response | Citrate cycle | hsa00020 | ||
Central carbon metabolism in cancer | hsa05230 | |||
Cell Process | Aerobic glycolysis | |||
Cell apoptosis | ||||
In-vitro Model | LN-18 | Glioblastoma | Homo sapiens | CVCL_0392 |
LN-229 | Glioblastoma | Homo sapiens | CVCL_0393 | |
SHG-44 | Astrocytoma | Homo sapiens | CVCL_6728 | |
U251 (Fibroblasts or fibroblast like cells) | ||||
U87 (A primary glioblastoma cell line) | ||||
Protein argonaute-1 (AGO1)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [11] | |||
Response Summary | loss of m6A RNA methylation and increased translation in human glioblastoma cells as well as a role for miRNAs in the modulation of m6A RNA demethylation in genes that are most efficiently translated during glioma stem cells differentiation. Ectopic expression of the RRACH-binding miR-145 induces loss of m6A, formation of FTO/Protein argonaute-1 (AGO1)/ILF3/miR-145 complexes on a clinically relevant tumor suppressor gene (CLIP3) and significant increase in its nascent translation. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
Target Regulation | Up regulation | |||
In-vitro Model | GBM1 | Glioblastoma | Homo sapiens | CVCL_DG57 |
GBM2 | Glioblastoma | Homo sapiens | CVCL_DG58 | |
GBM3 | Glioblastoma | Homo sapiens | CVCL_DG59 | |
Putative heat shock 70 kDa protein 7 (HSPA7)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [17] | |||
Response Summary | Putative heat shock 70 kDa protein 7 (HSPA7) promoted macrophage infiltration and SPP1 expression via upregulating the YAP1 and LOX expression of glioblastoma stem cells in vitro and in clinical glioblastoma tumor samples. HSPA7 is expected to predict the ability of PD-1 inhibitors to respond to treatment in glioblastoma. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Responsed Drug | Pembrolizumab | Approved | ||
Pathway Response | PD-L1 expression and PD-1 checkpoint pathway in cancer | hsa05235 | ||
In-vitro Model | A-172 | Glioblastoma | Homo sapiens | CVCL_0131 |
GSC 20 (Mesenchymal (MES) subtype GSC cell lines) | ||||
GSC 20 (Mesenchymal (MES) subtype GSC cell lines) | ||||
GSC 8-11 (Proneural (PN) subtype GSC cell lines) | ||||
LN-229 | Glioblastoma | Homo sapiens | CVCL_0393 | |
Neural progenitor cells (NPCs) (The progenitor cells of the CNS) | ||||
U-251MG | Astrocytoma | Homo sapiens | CVCL_0021 | |
U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 | |
Receptor-type tyrosine-protein phosphatase C (CD45)
In total 2 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [3] | |||
Response Summary | HNRNPA2B1 and HNRNPC were extensively expressed in the Glioblastoma multiforme(GBM) microenvironment.m6A regulators promoted the stemness state in GBM cancer cells. Cell communication analysis identified genes in the GALECTIN signaling network in GBM samples, and expression of these genes (LGALS9, CD44, Receptor-type tyrosine-protein phosphatase C (CD45), and HAVCR2) correlated with that of m6A regulators. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) | READER | ||
In-vitro Model | U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 |
THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene | [3] | |||
Response Summary | HNRNPA2B1 and HNRNPC were extensively expressed in the Glioblastoma multiforme(GBM) microenvironment. m6A regulators promoted the stemness state in GBM cancer cells. Cell communication analysis identified genes in the GALECTIN signaling network in GBM samples, and expression of these genes (LGALS9, CD44, Receptor-type tyrosine-protein phosphatase C (CD45), and HAVCR2) correlated with that of m6A regulators. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC) | READER | ||
In-vitro Model | U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 |
THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
Serine/arginine-rich splicing factor 11 (SRSF11)
In total 2 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [18] | |||
Response Summary | Silencing METTL3 or overexpressing dominant-negative mutant METTL3 suppressed the growth and self-renewal of Glioblastoma cells. Integrated transcriptome and MeRIP-seq analyses revealed that downregulating the expression of METTL3 decreased m6A modification levels of Serine/arginine-rich splicing factor 11 (SRSF11), which led to YTHDC1-dependent NMD of SRSF transcripts and decreased SRSF protein expression. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Up regulation | |||
Pathway Response | RNA degradation | hsa03018 | ||
Cell Process | mRNA decay | |||
In-vitro Model | U251 (Fibroblasts or fibroblast like cells) | |||
U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 | |
In-vivo Model | For subcutaneous tumor model, each mouse was injected subcutaneously in the right flank with 2 × 106 U87MG cells (METTL3-KD or control) in 100 uL PBS. | |||
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene | [18] | |||
Response Summary | Silencing METTL3 or overexpressing dominant-negative mutant METTL3 suppressed the growth and self-renewal of Glioblastoma cells. Integrated transcriptome and MeRIP-seq analyses revealed that downregulating the expression of METTL3 decreased m6A modification levels of Serine/arginine-rich splicing factor 11 (SRSF11), which led to YTHDC1-dependent NMD of SRSF transcripts and decreased SRSF protein expression. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | YTH domain-containing protein 1 (YTHDC1) | READER | ||
Target Regulation | Up regulation | |||
Pathway Response | RNA degradation | hsa03018 | ||
Cell Process | mRNA decay | |||
In-vitro Model | U251 (Fibroblasts or fibroblast like cells) | |||
U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 | |
In-vivo Model | For subcutaneous tumor model, each mouse was injected subcutaneously in the right flank with 2 × 106 U87MG cells (METTL3-KD or control) in 100 uL PBS. | |||
Serine/arginine-rich splicing factor 3 (SRSF3)
In total 2 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [18] | |||
Response Summary | Silencing METTL3 or overexpressing dominant-negative mutant METTL3 suppressed the growth and self-renewal of Glioblastoma cells. Integrated transcriptome and MeRIP-seq analyses revealed that downregulating the expression of METTL3 decreased m6A modification levels of Serine/arginine-rich splicing factor 3 (SRSF3), which led to YTHDC1-dependent NMD of SRSF transcripts and decreased SRSF protein expression. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Up regulation | |||
Pathway Response | RNA degradation | hsa03018 | ||
Cell Process | mRNA decay | |||
In-vitro Model | U251 (Fibroblasts or fibroblast like cells) | |||
U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 | |
In-vivo Model | For subcutaneous tumor model, each mouse was injected subcutaneously in the right flank with 2 × 106 U87MG cells (METTL3-KD or control) in 100 uL PBS. | |||
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene | [18] | |||
Response Summary | Silencing METTL3 or overexpressing dominant-negative mutant METTL3 suppressed the growth and self-renewal of Glioblastoma cells. Integrated transcriptome and MeRIP-seq analyses revealed that downregulating the expression of METTL3 decreased m6A modification levels of Serine/arginine-rich splicing factor 3 (SRSF3), which led to YTHDC1-dependent NMD of SRSF transcripts and decreased SRSF protein expression. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | YTH domain-containing protein 1 (YTHDC1) | READER | ||
Target Regulation | Up regulation | |||
Pathway Response | RNA degradation | hsa03018 | ||
Cell Process | mRNA decay | |||
In-vitro Model | U251 (Fibroblasts or fibroblast like cells) | |||
U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 | |
In-vivo Model | For subcutaneous tumor model, each mouse was injected subcutaneously in the right flank with 2 × 106 U87MG cells (METTL3-KD or control) in 100 uL PBS. | |||
Serine/arginine-rich splicing factor 6 (SRSF6)
In total 2 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [18] | |||
Response Summary | Silencing METTL3 or overexpressing dominant-negative mutant METTL3 suppressed the growth and self-renewal of Glioblastoma cells. Integrated transcriptome and MeRIP-seq analyses revealed that downregulating the expression of METTL3 decreased m6A modification levels of Serine/arginine-rich splicing factor 6 (SRSF6), which led to YTHDC1-dependent NMD of SRSF transcripts and decreased SRSF protein expression. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Up regulation | |||
Pathway Response | RNA degradation | hsa03018 | ||
Cell Process | mRNA decay | |||
In-vitro Model | U251 (Fibroblasts or fibroblast like cells) | |||
U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 | |
In-vivo Model | For subcutaneous tumor model, each mouse was injected subcutaneously in the right flank with 2 × 106 U87MG cells (METTL3-KD or control) in 100 uL PBS. | |||
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene | [18] | |||
Response Summary | Silencing METTL3 or overexpressing dominant-negative mutant METTL3 suppressed the growth and self-renewal of Glioblastoma cells. Integrated transcriptome and MeRIP-seq analyses revealed that downregulating the expression of METTL3 decreased m6A modification levels of Serine/arginine-rich splicing factor 6 (SRSF6), which led to YTHDC1-dependent NMD of SRSF transcripts and decreased SRSF protein expression. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | YTH domain-containing protein 1 (YTHDC1) | READER | ||
Target Regulation | Up regulation | |||
Pathway Response | RNA degradation | hsa03018 | ||
Cell Process | mRNA decay | |||
In-vitro Model | U251 (Fibroblasts or fibroblast like cells) | |||
U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 | |
In-vivo Model | For subcutaneous tumor model, each mouse was injected subcutaneously in the right flank with 2 × 106 U87MG cells (METTL3-KD or control) in 100 uL PBS. | |||
Serine/arginine-rich splicing factor 7 (SRSF7)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [19] | |||
Response Summary | The gene expression of Serine/arginine-rich splicing factor 7 (SRSF7) is positively correlated with glioblastoma (GBM) cell-specific m6A methylation. The two m6A sites on PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by IGF2BP2. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) | READER | ||
Pathway Response | Spliceosome | hsa03040 | ||
In-vitro Model | HEK293T | Normal | Homo sapiens | CVCL_0063 |
U87MG (Astroblastoma cells from human brain) | ||||
LN-229 | Glioblastoma | Homo sapiens | CVCL_0393 | |
A-172 | Glioblastoma | Homo sapiens | CVCL_0131 | |
LN-18 | Glioblastoma | Homo sapiens | CVCL_0392 | |
LN-428 | Glioblastoma | Homo sapiens | CVCL_3959 | |
LN-443 | Glioblastoma | Homo sapiens | CVCL_3960 | |
SNB-19 | Astrocytoma | Homo sapiens | CVCL_0535 | |
T98G | Glioblastoma | Homo sapiens | CVCL_0556 | |
U-118MG | Astrocytoma | Homo sapiens | CVCL_0633 | |
U251 (Fibroblasts or fibroblast like cells) | ||||
U-138MG | Astrocytoma | Homo sapiens | CVCL_0020 | |
Suppressor of cytokine signaling 2 (SOCS2)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [20] | |||
Response Summary | miR-302a was identified to target METTL3, which could inhibit Suppressor of cytokine signaling 2 (SOCS2) expression via m6A modification in glioma. | |||
Responsed Disease | Glioma [ICD-11: 2A00.0] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Down regulation | |||
Pathway Response | Transcriptional misregulation in cancer | hsa05202 | ||
Cell Process | RNA stability | |||
In-vitro Model | LN-229 | Glioblastoma | Homo sapiens | CVCL_0393 |
LN-18 | Glioblastoma | Homo sapiens | CVCL_0392 | |
HEB (human normal glial cell line HEB were obtained from Tongpai (Shanghai) biotechnology co., LTD (Shanghai, China)) | ||||
In-vivo Model | Mice were subcutaneously injected with 2.5 × 106 U251 cells stably infected with OE-NC, OE-JMJD1C, OE-NC and sh-NC, OE-JMJD1C and sh-NC or OE-JMJD1C and sh-SOCS2 (n = 10 in each group) in 0.1 ml PBS. | |||
TNF alpha-induced protein 3 (TNFAIP3)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [6] | |||
Response Summary | YTHDF2 enhanced TMZ resistance in GBM by activation of the PI3K/Akt and NF-Kappa-B signalling pathways via inhibition of EPHB3 and TNF alpha-induced protein 3 (TNFAIP3). | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Responsed Drug | Temozolomide | Approved | ||
Target Regulator | YTH domain-containing family protein 2 (YTHDF2) | READER | ||
Target Regulation | Down regulation | |||
Pathway Response | PI3K-Akt signaling pathway | hsa04151 | ||
Cell Process | RNA stability | |||
In-vitro Model | T98G | Glioblastoma | Homo sapiens | CVCL_0556 |
LN-229 | Glioblastoma | Homo sapiens | CVCL_0393 | |
In-vivo Model | 5 × 106 infected T98G cells (LV-NC or LV-YTHDF2) were injected into the flanks of mice through subcutaneous. | |||
Transcription factor HIVEP2 (HIVEP2)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [15] | |||
Response Summary | YTHDF2 facilitates m6A-dependent mRNA decay of LXRA and Transcription factor HIVEP2 (HIVEP2), which impacts the glioma patient survival. YTHDF2 promotes tumorigenesis of GBM cells, largely through the downregulation of LXRA and HIVEP2. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | YTH domain-containing family protein 2 (YTHDF2) | READER | ||
Target Regulation | Down regulation | |||
Pathway Response | mRNA surveillance pathway | hsa03015), RNA degradation | ||
Cell Process | RNA stability | |||
In-vitro Model | U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 |
U-251MG | Astrocytoma | Homo sapiens | CVCL_0021 | |
T98G | Glioblastoma | Homo sapiens | CVCL_0556 | |
SW1783 | Anaplastic astrocytoma | Homo sapiens | CVCL_1722 | |
LN-229 | Glioblastoma | Homo sapiens | CVCL_0393 | |
Hs 683 | Oligodendroglioma | Homo sapiens | CVCL_0844 | |
GSC7-2 (GSC7-2 were obtained from fresh surgical specimens of human primary and recurrent glioma) | ||||
GSC6-27 (GSC6-27 were obtained from fresh surgical specimens of human primary and recurrent glioma) | ||||
GSC23 | Glioblastoma | Homo sapiens | CVCL_DR59 | |
GSC20 (GSC20 were obtained from fresh surgical specimens of human primary and recurrent glioma) | ||||
GSC17 | Glioblastoma | Homo sapiens | CVCL_DR57 | |
GSC11 | Glioblastoma | Homo sapiens | CVCL_DR55 | |
In-vivo Model | For the studies of investigating mice survival, mice were intracranially injected with 10,000 GSC11, 10,000 GSC7-2, or 500,000 LN229 cells. | |||
Transcription factor PU.1 (SPI1)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [21] | |||
Response Summary | FTO inhibited growth, migration and invasion of GBM cells in vitro and in vivo.decreased FTO expression could induce the downregulation of MTMR3 expression by modulating the processing of pri-miR-10a in an m6A/HNRNPA2B1-dependent manner in GBM cells. Furthermore, the transcriptional activity of FTO was inhibited by the transcription factor Transcription factor PU.1 (SPI1). | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
Target Regulation | Down regulation | |||
In-vitro Model | U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 |
U251 (Fibroblasts or fibroblast like cells) | ||||
U-118MG | Astrocytoma | Homo sapiens | CVCL_0633 | |
LN-229 | Glioblastoma | Homo sapiens | CVCL_0393 | |
A-172 | Glioblastoma | Homo sapiens | CVCL_0131 | |
In-vivo Model | BALB/c male nude mice were 4 weeks old. GBM cells with stable overexpression or knockdown of FTO and ovNC or shNC were transduced with lentivirus expressing luciferase. The cells were intracranially injected at a density of 5 × 105/10 uL into every mouse to form an orthotopic xenograft model. Coordinates of injection were 1 mm anterior and 2.5 mm right to the bregma, at a depth of 3.5 mm (the right frontal lobes of the mouse). Every 6 days, bioluminescence imaging (IVIS Lumina Series III; PerkinElmer, Waltham, MA) was used to image the mouse. At 8 days, we randomly chose 5 mice from each group to euthanize them, and their brain tissues were fixed with paraformaldehyde for further study. Another 5 mice were used for survival time analysis. For DB2313 (563801; MedKoo) anti-tumor research, male nude mice were subcutaneously injected with 5 × 106 U87MG cells suspended in 0.1 mL PBS. After 7 days, mice were intraperitoneally injected with DB2313 at density of 10 mg/kg/day dissolved in PBS solvent containing 10% DMSO for 7 days. The other group treated with vehicle only was set as the control group. | |||
Transcription factor SOX-2 (SOX2)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [22] | |||
Response Summary | GBM tumors have elevated levels of METTL3 transcripts and silencing METTL3 in U87/TIC inhibited tumor growth in an intracranial orthotopic mouse model with prolonged mice survival. The exogenous overexpression of 3'UTR-less Transcription factor SOX-2 (SOX2) significantly alleviated the inhibition of neurosphere formation observed in METTL3 silenced GSCs. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Up regulation | |||
Pathway Response | Signaling pathways regulating pluripotency of stem cells | hsa04550 | ||
Cell Process | DNA repair | |||
Nucleotide excision repair (hsa03420) | ||||
In-vitro Model | Mouse immortalized astrocytes (A type of glial cell) | |||
UBX domain-containing protein 1 (UBXN1)
In total 2 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [14] | |||
Response Summary | YTHDF2 accelerated UBX domain-containing protein 1 (UBXN1) mRNA degradation via METTL3-mediated m6A, which, in turn, promoted NF-Kappa-B activation. YTHDF2 promotes the malignant progression of gliomas and revealed important insight into the upstream regulatory mechanism of NF-Kappa-B activation via UBXN1 with a primary focus on m6A modification. | |||
Responsed Disease | Glioma [ICD-11: 2A00.0] | |||
Target Regulator | YTH domain-containing family protein 2 (YTHDF2) | READER | ||
Target Regulation | Down regulation | |||
Pathway Response | NF-kappa B signaling pathway | hsa04064 | ||
In-vitro Model | U87 (A primary glioblastoma cell line) | |||
N33 (The GBM patient-derived cell line) | ||||
LN-229 | Glioblastoma | Homo sapiens | CVCL_0393 | |
H4 | Astrocytoma | Homo sapiens | CVCL_1239 | |
In-vivo Model | Five-week-old female BALB/c nude mice (Charles Rivers, Beijing, China) were selected for the experiments. U87 cells (5 × 105) transfected with an empty vector, YTHDF2 overexpression, or METTL3 overexpression vectors were suspended in PBS and injected into the right frontal node of nude mice. The inoculation position was 2 mm lateral and 2 mm posterior to the anterior fontanel. Tumor size was estimated from luciferase volume measurements and MRI. The mice were sacrificed when they exhibited disturbed activity or convulsion. The brain was then harvested and embedded in paraffin. | |||
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene | [14] | |||
Response Summary | YTHDF2 accelerated UBX domain-containing protein 1 (UBXN1) mRNA degradation via METTL3-mediated m6A, which, in turn, promoted NF-Kappa-B activation. YTHDF2 promotes the malignant progression of gliomas and revealed important insight into the upstream regulatory mechanism of NF-Kappa-B activation via UBXN1 with a primary focus on m6A modification. | |||
Responsed Disease | Glioma [ICD-11: 2A00.0] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Down regulation | |||
Pathway Response | NF-kappa B signaling pathway | hsa04064 | ||
In-vitro Model | U87 (A primary glioblastoma cell line) | |||
N33 (The GBM patient-derived cell line) | ||||
LN-229 | Glioblastoma | Homo sapiens | CVCL_0393 | |
H4 | Astrocytoma | Homo sapiens | CVCL_1239 | |
In-vivo Model | Five-week-old female BALB/c nude mice (Charles Rivers, Beijing, China) were selected for the experiments. U87 cells (5 × 105) transfected with an empty vector, YTHDF2 overexpression, or METTL3 overexpression vectors were suspended in PBS and injected into the right frontal node of nude mice. The inoculation position was 2 mm lateral and 2 mm posterior to the anterior fontanel. Tumor size was estimated from luciferase volume measurements and MRI. The mice were sacrificed when they exhibited disturbed activity or convulsion. The brain was then harvested and embedded in paraffin. | |||
Vacuolar protein-sorting-associated protein 25 (VPS25)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [23] | |||
Response Summary | YTHDC1 inhibited glioma proliferation by reducing the expression of Vacuolar protein-sorting-associated protein 25 (VPS25). | |||
Responsed Disease | Glioma [ICD-11: 2A00.0] | |||
Target Regulator | YTH domain-containing protein 1 (YTHDC1) | READER | ||
Target Regulation | Down regulation | |||
Pathway Response | JAK-STAT signaling pathway | hsa04630 | ||
Cell Process | Arrest cell cycle at G0/G1 phase | |||
Cell apoptosis | ||||
In-vitro Model | U251 (Fibroblasts or fibroblast like cells) | |||
U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 | |
In-vivo Model | The U87MG cells (1 × 107 cells in 0.1 ml PBS) were injected subcutaneously into BALB/c nude mice. Tumor width and length were recorded every 5 days. | |||
Cancer susceptibility 9 (CASC9)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [24] | |||
Response Summary | Cancer susceptibility 9 (CASC9)/IGF2BP2/HK2 axis promotes the aerobic glycolysis of glioblastoma multiforme. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) | READER | ||
Target Regulation | Up regulation | |||
Pathway Response | Glycolysis / Gluconeogenesis | hsa00010 | ||
Cell Process | Aerobic glycolysis | |||
In-vitro Model | NHA (Normal human astrocytes) | |||
U251 (Fibroblasts or fibroblast like cells) | ||||
U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 | |
Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [25] | |||
Response Summary | METTL3 promoted the malignant progression of IDH-wildtype gliomas and revealed important insight into the upstream regulatory mechanism of Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and NF-Kappa-B with a primary focus on m6A modification. | |||
Responsed Disease | Glioma [ICD-11: 2A00.0] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Up regulation | |||
Pathway Response | TNF signaling pathway | hsa04668 | ||
Cell Process | Cell proliferation and metastasis | |||
In-vitro Model | H4 | Astrocytoma | Homo sapiens | CVCL_1239 |
LN-229 | Glioblastoma | Homo sapiens | CVCL_0393 | |
U87 (A primary glioblastoma cell line) | ||||
In-vivo Model | U87 cells (5 × 105) transfected with an empty vector, METTL3 shRNA, or METTL3 overexpression vector were inoculated into the right frontal node of nude mice. | |||
Nuclear paraspeckle assembly transcript 1 (NEAT1)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [26] | |||
Response Summary | Hypoxia-induced ALKBH5 erased m6A deposition from the lncRNA NEAT1, stabilizing the transcript and facilitating Nuclear paraspeckle assembly transcript 1 (NEAT1)-mediated paraspeckle assembly. Ectopic expression of CXCL8 in ALKBH5-deficient glioblastoma multiforme cells partially restored TAM recruitment and tumor progression. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | RNA demethylase ALKBH5 (ALKBH5) | ERASER | ||
Target Regulation | Down regulation | |||
Pathway Response | Transcriptional misregulation in cancer | hsa05202 | ||
Cell Process | Immune | |||
In-vitro Model | GL261 | Mouse glioblastoma | Mus musculus | CVCL_Y003 |
U87 (A primary glioblastoma cell line) | ||||
In-vivo Model | Male C57BL/6 mice (4-6 weeks old) were used in all tumor allografting experiments and transplanted with GL261-luc cells (1×105) into the frontal lobes of brains. | |||
microRNA 145 (MIR145)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [11] | |||
Response Summary | loss of m6A RNA methylation and increased translation in human glioblastoma cells as well as a role for miRNAs in the modulation of m6A RNA demethylation in genes that are most efficiently translated during glioma stem cells differentiation. Ectopic expression of the RRACH-binding miR-145 induces loss of m6A, formation of FTO/AGO1/ILF3/microRNA 145 (MIR145) complexes on a clinically relevant tumor suppressor gene (CLIP3) and significant increase in its nascent translation. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
Target Regulation | Up regulation | |||
In-vitro Model | GBM1 | Glioblastoma | Homo sapiens | CVCL_DG57 |
GBM2 | Glioblastoma | Homo sapiens | CVCL_DG58 | |
GBM3 | Glioblastoma | Homo sapiens | CVCL_DG59 | |
microRNA 155 (MIR155)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [27] | |||
Response Summary | FTO Inhibition Enhances the Antitumor Effect of Temozolomide by Targeting MYC-microRNA 155 (MIR155)/miR-23a Cluster-MXI1 Feedback Circuit in Glioma. | |||
Responsed Disease | Glioma [ICD-11: 2A00.0] | |||
Responsed Drug | Temozolomide | Approved | ||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
In-vitro Model | A-172 | Glioblastoma | Homo sapiens | CVCL_0131 |
HEK293T | Normal | Homo sapiens | CVCL_0063 | |
U251 (Fibroblasts or fibroblast like cells) | ||||
U87 (A primary glioblastoma cell line) | ||||
In-vivo Model | Previously prepared U87 cells (5 × 106 cells, 60 uL) stably infected with miRNA were injected subcutaneously in the right flank of the mice, whereas control U87 cells infected with empty vector were injected in the left flank. | |||
microRNA 23a (MIR23A)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [27] | |||
Response Summary | FTO Inhibition Enhances the Antitumor Effect of Temozolomide by Targeting MYC-miR-155/microRNA 23a (MIR23A) Cluster-MXI1 Feedback Circuit in Glioma. | |||
Responsed Disease | Glioma [ICD-11: 2A00.0] | |||
Responsed Drug | Temozolomide | Approved | ||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
In-vitro Model | A-172 | Glioblastoma | Homo sapiens | CVCL_0131 |
HEK293T | Normal | Homo sapiens | CVCL_0063 | |
U251 (Fibroblasts or fibroblast like cells) | ||||
U87 (A primary glioblastoma cell line) | ||||
In-vivo Model | Previously prepared U87 cells (5 × 106 cells, 60 uL) stably infected with miRNA were injected subcutaneously in the right flank of the mice, whereas control U87 cells infected with empty vector were injected in the left flank. | |||
hsa-miR-671-5p
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [1] | |||
Response Summary | METTL3-mediated m6A modification upregulated circDLC1 expression, and circDLC1 promoted CTNNBIP1 transcription by sponging hsa-miR-671-5p, thus repressing the malignant proliferation of glioma. | |||
Responsed Disease | Glioma [ICD-11: 2A00.0] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Up regulation | |||
In-vitro Model | T98G | Glioblastoma | Homo sapiens | CVCL_0556 |
LN-229 | Glioblastoma | Homo sapiens | CVCL_0393 | |
LN-18 | Glioblastoma | Homo sapiens | CVCL_0392 | |
HEB (human normal glial cell line HEB were obtained from Tongpai (Shanghai) biotechnology co., LTD (Shanghai, China)) | ||||
A-172 | Glioblastoma | Homo sapiens | CVCL_0131 | |
Circ_DLC1
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [1] | |||
Response Summary | METTL3-mediated m6A modification upregulated Circ_DLC1 expression, and circDLC1 promoted CTNNBIP1 transcription by sponging miR-671-5p, thus repressing the malignant proliferation of glioma. | |||
Responsed Disease | Glioma [ICD-11: 2A00.0] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Up regulation | |||
In-vitro Model | T98G | Glioblastoma | Homo sapiens | CVCL_0556 |
LN-229 | Glioblastoma | Homo sapiens | CVCL_0393 | |
LN-18 | Glioblastoma | Homo sapiens | CVCL_0392 | |
HEB (human normal glial cell line HEB were obtained from Tongpai (Shanghai) biotechnology co., LTD (Shanghai, China)) | ||||
A-172 | Glioblastoma | Homo sapiens | CVCL_0131 | |
pri-miR-10a
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [21] | |||
Response Summary | FTO inhibited growth, migration and invasion of GBM cells in vitro and in vivo.decreased FTO expression could induce the downregulation of MTMR3 expression by modulating the processing of pri-miR-10a in an m6A/HNRNPA2B1-dependent manner in GBM cells. Furthermore, the transcriptional activity of FTO was inhibited by the transcription factor SPI1. | |||
Responsed Disease | Glioblastoma [ICD-11: 2A00.00] | |||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
Target Regulation | Up regulation | |||
In-vitro Model | U-87MG ATCC | Glioblastoma | Homo sapiens | CVCL_0022 |
U251 (Fibroblasts or fibroblast like cells) | ||||
U-118MG | Astrocytoma | Homo sapiens | CVCL_0633 | |
LN-229 | Glioblastoma | Homo sapiens | CVCL_0393 | |
A-172 | Glioblastoma | Homo sapiens | CVCL_0131 | |
In-vivo Model | BALB/c male nude mice were 4 weeks old. GBM cells with stable overexpression or knockdown of FTO and ovNC or shNC were transduced with lentivirus expressing luciferase. The cells were intracranially injected at a density of 5 × 105/10 uL into every mouse to form an orthotopic xenograft model. Coordinates of injection were 1 mm anterior and 2.5 mm right to the bregma, at a depth of 3.5 mm (the right frontal lobes of the mouse). Every 6 days, bioluminescence imaging (IVIS Lumina Series III; PerkinElmer, Waltham, MA) was used to image the mouse. At 8 days, we randomly chose 5 mice from each group to euthanize them, and their brain tissues were fixed with paraformaldehyde for further study. Another 5 mice were used for survival time analysis. For DB2313 (563801; MedKoo) anti-tumor research, male nude mice were subcutaneously injected with 5 × 106 U87MG cells suspended in 0.1 mL PBS. After 7 days, mice were intraperitoneally injected with DB2313 at density of 10 mg/kg/day dissolved in PBS solvent containing 10% DMSO for 7 days. The other group treated with vehicle only was set as the control group. | |||
References