m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00175)
Target Name RAC-alpha serine/threonine-protein kinase (AKT1)
Synonyms
Protein kinase B; PKB; Protein kinase B alpha; PKB alpha; Proto-oncogene c-Akt; RAC-PK-alpha; PKB; RAC
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Gene Name AKT1
Chromosomal Location 14q32.33
Family protein kinase superfamily; AGC Ser/Thr protein kinase family; RAC subfamily
Function
AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface (By similarity). Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling (By similarity). Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport . AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity (By similarity). Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven (By similarity). AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319' . FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis (By similarity). Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis (By similarity). Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity (By similarity). The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I). AKT mediates the antiapoptotic effects of IGF-I (By similarity). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development (By similarity). Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3. Phosphorylates STK3/MST2 at 'Thr-117' and 'Thr-384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation. Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation. Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity. Phosphorylation of BAD stimulates its pro-apoptotic activity. Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53. Phosphorylates palladin (PALLD), modulating cytoskeletal organization and cell motility. Phosphorylates prohibitin (PHB), playing an important role in cell metabolism and proliferation. Phosphorylates CDKN1A, for which phosphorylation at 'Thr-145' induces its release from CDK2 and cytoplasmic relocalization. These recent findings indicate that the AKT1 isoform has a more specific role in cell motility and proliferation. Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation. Phosphorylates PCK1 at 'Ser-90', reducing the binding affinity of PCK1 to oxaloacetate and changing PCK1 into an atypical protein kinase activity using GTP as donor. Also acts as an activator of TMEM175 potassium channel activity in response to growth factors: forms the lysoK(GF) complex together with TMEM175 and acts by promoting TMEM175 channel activation, independently of its protein kinase activity.
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Gene ID 207
Uniprot ID
AKT1_HUMAN
HGNC ID
HGNC:391
Ensembl Gene ID
ENSG00000142208
KEGG ID
hsa:207
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
AKT1 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).
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Methyltransferase-like 14 (METTL14) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL14
Cell Line Neural progenitor cell line Mus musculus
Treatment: METTL14 knockout NPCs
Control: Wild type NPCs
 GSE158985
Regulation
logFC: 8.08E-01
p-value: 3.19E-03
More Results Click to View More RNA-seq Results
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary The m6A modification level was decreased in GC and METTL14 was a key regulator resulting in m6A disorder in GC. METTL14 overexpression suppressed GC cell proliferation and aggression by deactivating the PI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR pathway and the EMT pathway, respectively.
Target Regulation Down regulation
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
mTOR signaling pathway hsa04150
In-vitro Model SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
GES-1 Normal Homo sapiens CVCL_EQ22
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary METTL14 was found to inhibit HCC cell migration, invasion, and EMT through modulating EGFR/PI3K/RAC-alpha serine/threonine-protein kinase (AKT1) signaling pathway in an m6A-dependent manner.
Target Regulation Down regulation
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Epithelial-mesenchymal transition
In-vitro Model YY-8103 Adult hepatocellular carcinoma Homo sapiens CVCL_WY40
SMMC-7721 Endocervical adenocarcinoma Homo sapiens CVCL_0534
HCCLM3 Adult hepatocellular carcinoma Homo sapiens CVCL_6832
L-02 Endocervical adenocarcinoma Homo sapiens CVCL_6926
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Hep 3B2.1-7 Childhood hepatocellular carcinoma Homo sapiens CVCL_0326
In-vivo Model For the lung metastasis model, stably transfected HepG2 cells (1 × 106/0.1 mL DMEM) were injected into each nude mouse through the tail vein. Five weeks later, mice were euthanized, and the lung tissues were collected.
Methyltransferase-like 3 (METTL3) [WRITER]
 Regulator Info 
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
 GSE198512
Regulation
logFC: 1.27E+00
p-value: 1.77E-02
More Results Click to View More RNA-seq Results
In total 10 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary METTL3 depletion in human myeloid leukemia cell lines induces cell differentiation and apoptosis and delays leukemia progression in recipient mice in vivo. Single-nucleotide-resolution mapping of m6A coupled with ribosome profiling reveals that m6A promotes the translation of c-MYC, BCL2 and PTEN mRNAs in the human acute myeloid leukemia MOLM-13 cell line. Moreover, loss of METTL3 leads to increased levels of phosphorylated RAC-alpha serine/threonine-protein kinase (AKT1).
Target Regulation Down regulation
Responsed Disease Acute myeloid leukaemia ICD-11: 2A60
 Disease Info 
Pathway Response Apoptosis hsa04210
Cell Process Cell differentiation and apoptosis
In-vitro Model HSPC (Human hematopoietic stem cell)
In-vivo Model 500,000 selected cells were injected via tail vein or retro-orbital route into female NSG (6-8 week old) recipient mice that had been sublethally irradiated with 475 cGy one day before transplantation.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [4]
Response Summary Downregulated METTL3 expression in AML-MSCs induced an increase in RAC-alpha serine/threonine-protein kinase (AKT1) protein, resulting in enhanced MSC adipogenesis, thereby contributing to chemoresistance in acute myeloid leukaemia (AML) cells.
Target Regulation Down regulation
Responsed Disease Acute myeloid leukaemia ICD-11: 2A60
 Disease Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Adipogenesis
In-vitro Model HL-60 Adult acute myeloid leukemia Homo sapiens CVCL_0002
U-937 Adult acute monocytic leukemia Homo sapiens CVCL_0007
THP-1 Childhood acute monocytic leukemia Homo sapiens CVCL_0006
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [5]
Response Summary METTL3 plays a carcinogenic role in human EC progression partially through RAC-alpha serine/threonine-protein kinase (AKT1) signaling pathways, suggesting that METTL3 serves as a potential therapeutic target for esophageal cancer therapy. A double-effect inhibitor (BEZ235) inhibited AKT and mTOR phosphorylation and hindered the effect of METTL3 overexpression on the proliferation and migration of Eca-109 and KY-SE150 cells.
Target Regulation Up regulation
Responsed Disease Esophageal cancer ICD-11: 2B70
 Disease Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
Wnt signaling pathway hsa04310
mTOR signaling pathway hsa04150
Apoptosis hsa04210
Cell Process Cell proliferation and invasion
Cell apoptosis
In-vitro Model Eca-109 Esophageal squamous cell carcinoma Homo sapiens CVCL_6898
KYSE-150 Esophageal squamous cell carcinoma Homo sapiens CVCL_1348
Normal esophageal epithelial cell line (HEEC) (Isolated from the human esophagus)
Experiment 4 Reporting the m6A Methylation Regulator of This Target Gene [6]
Response Summary Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Bcl2 and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of RAC-alpha serine/threonine-protein kinase (AKT1) and expression of down-stream effectors p70S6K and Cyclin D1.
Target Regulation Up regulation
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Pathway Response Apoptosis hsa04210
PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation
Cell migration
Cell invasion
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
Experiment 5 Reporting the m6A Methylation Regulator of This Target Gene [7]
Response Summary METTL3 contributes to the progression and chemoresistance of NSCLC by promoting RAC-alpha serine/threonine-protein kinase (AKT1) protein expression through regulating AKT1 mRNA m6A levels, and provides an efficient therapeutic intervention target for overcoming chemoresistance in NSCLC.
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Experiment 6 Reporting the m6A Methylation Regulator of This Target Gene [8]
Response Summary METTL3-mediated m6 A methylation promotes lung cancer progression via activating PI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR pathway.
Target Regulation Up regulation
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Pathway Response mTOR signaling pathway hsa04150
PI3K-Akt signaling pathway hsa04151
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
In-vivo Model 5 × 106 A549 cells overexpressing METTL3 (Lv-METTL3) or control (Lv-Ctrl) were suspended in 100?uL phosphate-buffered saline (PBS), and were subcutaneously injected into mouse lower right flank. Drug treatment started in the Lv-METTL3 group when the tumour volume reached around 100 mm3. Mice were randomly divided into three groups to receive vehicle, GSK2536771 (30 mg/kg) or rapamycin (1 mg/kg). Drugs were administrated daily through intraperitoneal injection for 18 days. Treatment conditions were chosen as previously reported.
Experiment 7 Reporting the m6A Methylation Regulator of This Target Gene [9]
Response Summary METTL3 knockdown downregulated the phosphorylation levels of RAC-alpha serine/threonine-protein kinase (AKT1) and the expression of the downstream effector Cyclin D1 in ovarian cancer.
Target Regulation Up regulation
Responsed Disease Ovarian cancer ICD-11: 2C73
 Disease Info 
Pathway Response Apoptosis hsa04210
PI3K-Akt signaling pathway hsa04151
Cell Process Cell cycle
Cell apoptosis
In-vitro Model OVCAR-3 Ovarian serous adenocarcinoma Homo sapiens CVCL_0465
SK-OV-3 Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
Experiment 8 Reporting the m6A Methylation Regulator of This Target Gene [10]
Response Summary Knock-down of YTHDF2 or METTL3 significantly induced the expression of LHPP and NKX3-1 at both mRNA and protein level with inhibited phosphorylated RAC-alpha serine/threonine-protein kinase (AKT1). YTHDF2 mediates the mRNA degradation of the tumor suppressors LHPP and NKX3-1 in m6A-dependent way to regulate AKT phosphorylation-induced tumor progression in prostate cancer.
Target Regulation Up regulation
Responsed Disease Prostate cancer ICD-11: 2C82
 Disease Info 
Pathway Response Oxidative phosphorylation hsa00190
In-vitro Model VCaP Prostate carcinoma Homo sapiens CVCL_2235
RWPE-1 Normal Homo sapiens CVCL_3791
PC-3 Prostate carcinoma Homo sapiens CVCL_0035
DU145 Prostate carcinoma Homo sapiens CVCL_0105
22Rv1 Prostate carcinoma Homo sapiens CVCL_1045
In-vivo Model Approximately 2 × 106 PCa cells (PC-3 shNC, shYTHDF2, shMETTL3 cell lines) per mouse suspended in 100 uL PBS were injected in the flank of male BALB/c nude mice (4 weeks old). During the 40-day observation, the tumor size (V = (width2×length ×0.52)) was measured with vernier caliper. Approximately 1.5 × 106 PCa cells suspended in 100 uL of PBS (PC-3 shNC, shYTHDF2, and shMETTL3 cell lines) per mouse were injected into the tail vein of male BALB/c nude mice (4 weeks old). The IVIS Spectrum animal imaging system (PerkinElmer) was used to evaluate the tumor growth (40 days) and whole metastasis conditions (4 weeks and 6 weeks) with 100 uL XenoLight D-luciferin Potassium Salt (15 mg/ml, Perkin Elmer) per mouse. Mice were anesthetized and then sacrificed for tumors and metastases which were sent for further organ-localized imaging as above, IHC staining and hematoxylin-eosin (H&E) staining.
Experiment 9 Reporting the m6A Methylation Regulator of This Target Gene [11]
Response Summary Knockdown of METTL3 could obviously promote cell proliferation, migration and invasion function, and induce G0/G1 arrest,METTL3 acts as a novel marker for tumorigenesis, development and survival of RCC. Knockdown of METTL3 promoted changes in pI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR markers' expression with a gain in p-PI3k, p-AKT, p-mTOR and p-p70, and a loss of p-4EBP1.
Target Regulation Down regulation
Responsed Disease Renal cell carcinoma ICD-11: 2C90
 Disease Info 
Cell Process Epithelial-to-mesenchymal transition
Arrest cell cycle at G0/G1 phase
In-vitro Model ACHN Papillary renal cell carcinoma Homo sapiens CVCL_1067
Caki-1 Clear cell renal cell carcinoma Homo sapiens CVCL_0234
Caki-2 Papillary renal cell carcinoma Homo sapiens CVCL_0235
HK2 Normal Acipenser baerii CVCL_YE28
In-vivo Model Cells (5×106 cells in 200 uL) were suspended with 100 uL PBS and 100 uL Matrigel Matrix, and injected subcutaneously into the left armpit of each mouse.
Experiment 10 Reporting the m6A Methylation Regulator of This Target Gene [12]
Response Summary METTL3 promotes the progression of retinoblastoma through PI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR pathways in vitro and in vivo. METTL3 has an impact on the PI3K-AKT-mTOR-P70S6K/4EBP1 pathway. The cell proliferation results show that the stimulatory function of METTL3 is lost after rapamycin treatment.
Target Regulation Up regulation
Responsed Disease Retinoblastoma ICD-11: 2D02.2
 Disease Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
mTOR signaling pathway hsa04150
Apoptosis hsa04210
Cell Process Cell proliferation
Cell migration
Cell invasion
Cell apoptosis
In-vitro Model WERI-Rb-1 Retinoblastoma Homo sapiens CVCL_1792
Y-79 Retinoblastoma Homo sapiens CVCL_1893
In-vivo Model To establish a subcutaneous tumour model in nude mice, 2 × 107 Y79 cells (METTL3 knockdown group: shNC, shRNA1 and shRNA2; METTL3 up-regulated group: NC and METLL3) were resuspended in 1 mL of pre-cooled PBS, and 200 uL of the cell suspension was injected subcutaneously into the left side of the armpit to investigate tumour growth (4 × 106 per mouse).
RNA demethylase ALKBH5 (ALKBH5) [ERASER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5
Cell Line 143B cell line Homo sapiens
Treatment: siALKBH5 transfected 143B cells
Control: siControl 143B cells
 GSE154528
Regulation
logFC: -9.73E-01
p-value: 3.10E-07
More Results Click to View More RNA-seq Results
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [13]
Response Summary ALKBH5-mediated m6A demethylation enhanced the stability of KCNK15-AS1. In pancreatic cancer, KCNK15-AS1 bound to KCNK15 to inhibit its translation, and interacted with MDM2 to induce REST ubiquitination, which eventually facilitated PTEN transcription to inactivate RAC-alpha serine/threonine-protein kinase (AKT1) pathway.
Responsed Disease Pancreatic cancer ICD-11: 2C10
 Disease Info 
Pathway Response Apoptosis hsa04210
PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation
Cell migration
Epithelial-mesenchymal transition
Cell apoptosis
In-vitro Model BxPC-3 Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0186
CFPAC-1 Cystic fibrosis Homo sapiens CVCL_1119
MIA PaCa-2 Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0428
PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [14]
Response Summary The overexpression of ALKBH5 led to the activation of RAC-alpha serine/threonine-protein kinase (AKT1), and BMP2 was regulated by ALKBH5 through the AKT signaling pathway. ALKBH5 promoted the osteogenesis of the ligamentum flavum cells through BMP2 demethylation and AKT activation. MK22606 is an AKT inhibitor. Moreover, when ALKBH5 was knocked down in the ligamentum flavum cells, p-AKT was inhibited when compared with that in the overexpressed ALKBH5 and control groups.
Target Regulation Up regulation
Responsed Disease Ossification of spinal ligaments ICD-11: FA83
 Disease Info 
Responsed Drug MK22606 Investigative
 Drug Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Ossification
In-vitro Model Ligamentum flavum cells (Ligamentum flavum cells)
YTH domain-containing family protein 1 (YTHDF1) [READER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1
Cell Line AGS cell line Homo sapiens
Treatment: shYTHDF1 AGS
Control: shNC AGS
 GSE166972
Regulation
logFC: -2.24E+00
p-value: 7.14E-03
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [15]
Response Summary YTHDF1 contributes to the progression of HCC by activating PI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR signaling pathway and inducing EMT.
Target Regulation Down regulation
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
mTOR signaling pathway hsa04150
Cell Process Epithelial-mesenchymal transition
Cell migration
Cell invasion
Cell proliferation
In-vitro Model SNU-398 Adult hepatocellular carcinoma Homo sapiens CVCL_0077
SK-HEP-1 Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
PLC/PRF/5 Adult hepatocellular carcinoma Homo sapiens CVCL_0485
L-02 Endocervical adenocarcinoma Homo sapiens CVCL_6926
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Hep 3B2.1-7 Childhood hepatocellular carcinoma Homo sapiens CVCL_0326
HEK293T Normal Homo sapiens CVCL_0063
HCCLM3 Adult hepatocellular carcinoma Homo sapiens CVCL_6832
In-vivo Model Ten four-week-old BALB/c male nude mice (GemPharmatech, Jiangsu, China) were subcutaneously injected with control Huh7 cells 2 × 106 (left-back) and stable knockdown of YTHDF1 Huh7 cells 2 × 106 (right-back). These cells were respectively premixed with 50 ul Matrigel (Corning, 354,234) in 100 ul PBS.
Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) [READER]
 Regulator Info 
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [16]
Response Summary In breast cancer, modest stable overexpression of A2B1 in MCF-7 cells (MCF-7-A2B1 cells) resulted in tamoxifen and fulvestrant- resistance whereas knockdown of A2B1 in LCC9 and LY2 cells restored tamoxifen and fulvestrant, endocrine-sensitivity. MCF-7-A2B1 cells have increased ER-alpha and reduced miR-222-3p that targets ER-alpha. MCF-7-A2B1 have activated RAC-alpha serine/threonine-protein kinase (AKT1) and MAPK that depend on A2B1 expression and are growth inhibited by inhibitors of these pathways.
Target Regulation Up regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Drug Fulvestrant Approved
 Drug Info 
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Cell Process Cell migration and invasion
In-vitro Model HCC1806 Breast squamous cell carcinoma Homo sapiens CVCL_1258
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [16]
Response Summary In breast cancer, modest stable overexpression of A2B1 in MCF-7 cells (MCF-7-A2B1 cells) resulted in tamoxifen and fulvestrant - resistance whereas knockdown of A2B1 in LCC9 and LY2 cells restored tamoxifen and fulvestrant, endocrine-sensitivity. MCF-7-A2B1 cells have increased ER-alpha and reduced miR-222-3p that targets ER-alpha. MCF-7-A2B1 have activated RAC-alpha serine/threonine-protein kinase (AKT1) and MAPK that depend on A2B1 expression and are growth inhibited by inhibitors of these pathways.
Target Regulation Up regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Drug Tamoxifen Approved
 Drug Info 
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Cell Process Cell migration and invasion
In-vitro Model HCC1806 Breast squamous cell carcinoma Homo sapiens CVCL_1258
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [17]
Response Summary N6-methyladenosine (m6A) methylation modification is implicated in the pathogenesis of lung ischemia-reperfusion injury. YTHDF3 or IGF2BP2 knockdown inhibited hypoxia/reoxygenation-activated p38, ERK1/2, RAC-alpha serine/threonine-protein kinase (AKT1), and NF-Kappa-B pathways in BEAS-2B cells, and inhibited p-p65, IL-1-beta and TNF-alpha secretion.
Target Regulation Up regulation
Responsed Disease Gangrene or necrosis of lung ICD-11: CA43
 Disease Info 
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Apoptosis hsa04210
Cell Process Biological regulation
Cell apoptosis
In-vitro Model BEAS-2B Normal Homo sapiens CVCL_0168
In-vivo Model After being anesthetized with urethane (i.p.), SD rats were endotracheally intubated and ventilated using an animal ventilator under the conditions: respiratory rate of 70 breaths/min, tidal volume of 20 ml/kg, and inspiratory/expiratory ratio of 1:1.
YTH domain-containing family protein 2 (YTHDF2) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [10]
Response Summary Knock-down of YTHDF2 or METTL3 significantly induced the expression of LHPP and NKX3-1 at both mRNA and protein level with inhibited phosphorylated RAC-alpha serine/threonine-protein kinase (AKT1). YTHDF2 mediates the mRNA degradation of the tumor suppressors LHPP and NKX3-1 in m6A-dependent way to regulate AKT phosphorylation-induced tumor progression in prostate cancer.
Target Regulation Up regulation
Responsed Disease Prostate cancer ICD-11: 2C82
 Disease Info 
Pathway Response Oxidative phosphorylation hsa00190
In-vitro Model VCaP Prostate carcinoma Homo sapiens CVCL_2235
RWPE-1 Normal Homo sapiens CVCL_3791
PC-3 Prostate carcinoma Homo sapiens CVCL_0035
DU145 Prostate carcinoma Homo sapiens CVCL_0105
22Rv1 Prostate carcinoma Homo sapiens CVCL_1045
YTH domain-containing family protein 3 (YTHDF3) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [17]
Response Summary N6-methyladenosine (m6A) methylation modification is implicated in the pathogenesis of lung ischemia-reperfusion injury. YTHDF3 or IGF2BP2 knockdown inhibited hypoxia/reoxygenation-activated p38, ERK1/2, RAC-alpha serine/threonine-protein kinase (AKT1), and NF-Kappa-B pathways in BEAS-2B cells, and inhibited p-p65, IL-1-beta and TNF-alpha secretion.
Target Regulation Up regulation
Responsed Disease Gangrene or necrosis of lung ICD-11: CA43
 Disease Info 
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Apoptosis hsa04210
Cell Process Biological regulation
Cell apoptosis
In-vitro Model BEAS-2B Normal Homo sapiens CVCL_0168
In-vivo Model After being anesthetized with urethane (i.p.), SD rats were endotracheally intubated and ventilated using an animal ventilator under the conditions: respiratory rate of 70 breaths/min, tidal volume of 20 ml/kg, and inspiratory/expiratory ratio of 1:1.
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 [18]
Response Summary YTHDC2 promotes radiotherapy resistance of NPC cells by activating the IGF1R/RAC-alpha serine/threonine-protein kinase (AKT1)/S6 signaling axis and serves as a potential therapeutic target in radiosensitization of NPC cells.
Target Regulation Up regulation
Responsed Disease Nasopharyngeal carcinoma ICD-11: 2B6B
 Disease Info 
In-vitro Model HK1-IRR (HK1-IRR (HK1-ionizing radiation radioresistent cell line) was derived from HK1 after a prolonged exposure of irradiation.HK1, a generous gift from Prof. Ya Cao (Cancer Research Institute, Central South University), was established from a recurrent nasopharynx carcinoma of a Chinese 17-year-old male patient)
NPC/HK1 Nasopharyngeal carcinoma Homo sapiens CVCL_7084
CNE2-IRR (CNE2-IRR (CNE2-ionizing radiation radioresistent cell line) was derived from CNE2 after a prolonged exposure of irradiation)
CNE-2 Nasopharyngeal carcinoma Homo sapiens CVCL_6889
In-vivo Model 2 × 106 cells resuspended in 50 uL of Matrigel (Corning) were subcutaneously injected into 4-6 weeks old male nude mice. When tumor volumes reached 150-200 mm3, animals were divided into control group and radiotherapy group. In the radiotherapy group, tumors were treated with a single irradiation (4 Gy) when tumor volumes reached approximately 150-200 mm3. The tumor stopped growing in the next few days and then restarted growth.
Acute myeloid leukaemia [ICD-11: 2A60]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary METTL3 depletion in human myeloid leukemia cell lines induces cell differentiation and apoptosis and delays leukemia progression in recipient mice in vivo. Single-nucleotide-resolution mapping of m6A coupled with ribosome profiling reveals that m6A promotes the translation of c-MYC, BCL2 and PTEN mRNAs in the human acute myeloid leukemia MOLM-13 cell line. Moreover, loss of METTL3 leads to increased levels of phosphorylated RAC-alpha serine/threonine-protein kinase (AKT1).
Responsed Disease Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response Apoptosis hsa04210
Cell Process Cell differentiation and apoptosis
In-vitro Model HSPC (Human hematopoietic stem cell)
In-vivo Model 500,000 selected cells were injected via tail vein or retro-orbital route into female NSG (6-8 week old) recipient mice that had been sublethally irradiated with 475 cGy one day before transplantation.
Experiment 2 Reporting the m6A-centered Disease Response [4]
Response Summary Downregulated METTL3 expression in AML-MSCs induced an increase in RAC-alpha serine/threonine-protein kinase (AKT1) protein, resulting in enhanced MSC adipogenesis, thereby contributing to chemoresistance in acute myeloid leukaemia (AML) cells.
Responsed Disease Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Adipogenesis
In-vitro Model HL-60 Adult acute myeloid leukemia Homo sapiens CVCL_0002
U-937 Adult acute monocytic leukemia Homo sapiens CVCL_0007
THP-1 Childhood acute monocytic leukemia Homo sapiens CVCL_0006
Nasopharyngeal carcinoma [ICD-11: 2B6B]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [18]
Response Summary YTHDC2 promotes radiotherapy resistance of NPC cells by activating the IGF1R/RAC-alpha serine/threonine-protein kinase (AKT1)/S6 signaling axis and serves as a potential therapeutic target in radiosensitization of NPC cells.
Responsed Disease Nasopharyngeal carcinoma [ICD-11: 2B6B]
Target Regulator YTH domain-containing protein 2 (YTHDC2) READER
 Regulator Info 
Target Regulation Up regulation
In-vitro Model HK1-IRR (HK1-IRR (HK1-ionizing radiation radioresistent cell line) was derived from HK1 after a prolonged exposure of irradiation.HK1, a generous gift from Prof. Ya Cao (Cancer Research Institute, Central South University), was established from a recurrent nasopharynx carcinoma of a Chinese 17-year-old male patient)
NPC/HK1 Nasopharyngeal carcinoma Homo sapiens CVCL_7084
CNE2-IRR (CNE2-IRR (CNE2-ionizing radiation radioresistent cell line) was derived from CNE2 after a prolonged exposure of irradiation)
CNE-2 Nasopharyngeal carcinoma Homo sapiens CVCL_6889
In-vivo Model 2 × 106 cells resuspended in 50 uL of Matrigel (Corning) were subcutaneously injected into 4-6 weeks old male nude mice. When tumor volumes reached 150-200 mm3, animals were divided into control group and radiotherapy group. In the radiotherapy group, tumors were treated with a single irradiation (4 Gy) when tumor volumes reached approximately 150-200 mm3. The tumor stopped growing in the next few days and then restarted growth.
Esophageal cancer [ICD-11: 2B70]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [5]
Response Summary METTL3 plays a carcinogenic role in human EC progression partially through RAC-alpha serine/threonine-protein kinase (AKT1) signaling pathways, suggesting that METTL3 serves as a potential therapeutic target for esophageal cancer therapy. A double-effect inhibitor (BEZ235) inhibited AKT and mTOR phosphorylation and hindered the effect of METTL3 overexpression on the proliferation and migration of Eca-109 and KY-SE150 cells.
Responsed Disease Esophageal cancer [ICD-11: 2B70]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Wnt signaling pathway hsa04310
mTOR signaling pathway hsa04150
Apoptosis hsa04210
Cell Process Cell proliferation and invasion
Cell apoptosis
In-vitro Model Eca-109 Esophageal squamous cell carcinoma Homo sapiens CVCL_6898
KYSE-150 Esophageal squamous cell carcinoma Homo sapiens CVCL_1348
Normal esophageal epithelial cell line (HEEC) (Isolated from the human esophagus)
Gastric cancer [ICD-11: 2B72]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary The m6A modification level was decreased in GC and METTL14 was a key regulator resulting in m6A disorder in GC. METTL14 overexpression suppressed GC cell proliferation and aggression by deactivating the PI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR pathway and the EMT pathway, respectively.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
mTOR signaling pathway hsa04150
In-vitro Model SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
GES-1 Normal Homo sapiens CVCL_EQ22
Experiment 2 Reporting the m6A-centered Disease Response [6]
Response Summary Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Bcl2 and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of RAC-alpha serine/threonine-protein kinase (AKT1) and expression of down-stream effectors p70S6K and Cyclin D1.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Apoptosis hsa04210
PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation
Cell migration
Cell invasion
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
Pancreatic cancer [ICD-11: 2C10]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [13]
Response Summary ALKBH5-mediated m6A demethylation enhanced the stability of KCNK15-AS1. In pancreatic cancer, KCNK15-AS1 bound to KCNK15 to inhibit its translation, and interacted with MDM2 to induce REST ubiquitination, which eventually facilitated PTEN transcription to inactivate RAC-alpha serine/threonine-protein kinase (AKT1) pathway.
Responsed Disease Pancreatic cancer [ICD-11: 2C10]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
Pathway Response Apoptosis hsa04210
PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation
Cell migration
Epithelial-mesenchymal transition
Cell apoptosis
In-vitro Model BxPC-3 Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0186
CFPAC-1 Cystic fibrosis Homo sapiens CVCL_1119
MIA PaCa-2 Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0428
PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
Gastrointestinal cancer [ICD-11: 2C11]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response []
Response Summary m6A regulators were mostly upregulated in Gastrointestinal cancer and their differential expression significantly influenced the overall survival of patients with GI cancer. The phosphatidylinositol-3-kinase (PI3K)/RAC-alpha serine/threonine-protein kinase (AKT1) and mammalian target of rapamycin (mTOR) signaling pathways were found to be potentially affected by m6A modification in most human cancers, including GI cancer, which was further verified by m6A-Seq and phospho-MAPK array.
Responsed Disease Gastrointestinal cancer [ICD-11: 2C11]
Pathway Response PI3K-Akt signaling pathway hsa04151), mTOR signaling pathway
In-vitro Model ()
PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
()
Liver cancer [ICD-11: 2C12]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary METTL14 was found to inhibit HCC cell migration, invasion, and EMT through modulating EGFR/PI3K/RAC-alpha serine/threonine-protein kinase (AKT1) signaling pathway in an m6A-dependent manner.
Responsed Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Epithelial-mesenchymal transition
In-vitro Model YY-8103 Adult hepatocellular carcinoma Homo sapiens CVCL_WY40
SMMC-7721 Endocervical adenocarcinoma Homo sapiens CVCL_0534
HCCLM3 Adult hepatocellular carcinoma Homo sapiens CVCL_6832
L-02 Endocervical adenocarcinoma Homo sapiens CVCL_6926
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Hep 3B2.1-7 Childhood hepatocellular carcinoma Homo sapiens CVCL_0326
In-vivo Model For the lung metastasis model, stably transfected HepG2 cells (1 × 106/0.1 mL DMEM) were injected into each nude mouse through the tail vein. Five weeks later, mice were euthanized, and the lung tissues were collected.
Experiment 2 Reporting the m6A-centered Disease Response [15]
Response Summary YTHDF1 contributes to the progression of HCC by activating PI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR signaling pathway and inducing EMT.
Responsed Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Down regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
mTOR signaling pathway hsa04150
Cell Process Epithelial-mesenchymal transition
Cell migration
Cell invasion
Cell proliferation
In-vitro Model SNU-398 Adult hepatocellular carcinoma Homo sapiens CVCL_0077
SK-HEP-1 Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
PLC/PRF/5 Adult hepatocellular carcinoma Homo sapiens CVCL_0485
L-02 Endocervical adenocarcinoma Homo sapiens CVCL_6926
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Hep 3B2.1-7 Childhood hepatocellular carcinoma Homo sapiens CVCL_0326
HEK293T Normal Homo sapiens CVCL_0063
HCCLM3 Adult hepatocellular carcinoma Homo sapiens CVCL_6832
In-vivo Model Ten four-week-old BALB/c male nude mice (GemPharmatech, Jiangsu, China) were subcutaneously injected with control Huh7 cells 2 × 106 (left-back) and stable knockdown of YTHDF1 Huh7 cells 2 × 106 (right-back). These cells were respectively premixed with 50 ul Matrigel (Corning, 354,234) in 100 ul PBS.
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [7]
Response Summary METTL3 contributes to the progression and chemoresistance of NSCLC by promoting RAC-alpha serine/threonine-protein kinase (AKT1) protein expression through regulating AKT1 mRNA m6A levels, and provides an efficient therapeutic intervention target for overcoming chemoresistance in NSCLC.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Experiment 2 Reporting the m6A-centered Disease Response [8]
Response Summary METTL3-mediated m6 A methylation promotes lung cancer progression via activating PI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR pathway.
Responsed Disease Lung cancer [ICD-11: 2C25]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response mTOR signaling pathway hsa04150
PI3K-Akt signaling pathway hsa04151
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
In-vivo Model 5 × 106 A549 cells overexpressing METTL3 (Lv-METTL3) or control (Lv-Ctrl) were suspended in 100?uL phosphate-buffered saline (PBS), and were subcutaneously injected into mouse lower right flank. Drug treatment started in the Lv-METTL3 group when the tumour volume reached around 100 mm3. Mice were randomly divided into three groups to receive vehicle, GSK2536771 (30 mg/kg) or rapamycin (1 mg/kg). Drugs were administrated daily through intraperitoneal injection for 18 days. Treatment conditions were chosen as previously reported.
Breast cancer [ICD-11: 2C60]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [16]
Response Summary In breast cancer, modest stable overexpression of A2B1 in MCF-7 cells (MCF-7-A2B1 cells) resulted in tamoxifen and fulvestrant- resistance whereas knockdown of A2B1 in LCC9 and LY2 cells restored tamoxifen and fulvestrant, endocrine-sensitivity. MCF-7-A2B1 cells have increased ER-alpha and reduced miR-222-3p that targets ER-alpha. MCF-7-A2B1 have activated RAC-alpha serine/threonine-protein kinase (AKT1) and MAPK that depend on A2B1 expression and are growth inhibited by inhibitors of these pathways.
Responsed Disease Breast cancer [ICD-11: 2C60]
Target Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
 Regulator Info 
Target Regulation Up regulation
Responsed Drug Fulvestrant Approved
 Drug Info 
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Cell Process Cell migration and invasion
In-vitro Model HCC1806 Breast squamous cell carcinoma Homo sapiens CVCL_1258
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
Experiment 2 Reporting the m6A-centered Disease Response [16]
Response Summary In breast cancer, modest stable overexpression of A2B1 in MCF-7 cells (MCF-7-A2B1 cells) resulted in tamoxifen and fulvestrant - resistance whereas knockdown of A2B1 in LCC9 and LY2 cells restored tamoxifen and fulvestrant, endocrine-sensitivity. MCF-7-A2B1 cells have increased ER-alpha and reduced miR-222-3p that targets ER-alpha. MCF-7-A2B1 have activated RAC-alpha serine/threonine-protein kinase (AKT1) and MAPK that depend on A2B1 expression and are growth inhibited by inhibitors of these pathways.
Responsed Disease Breast cancer [ICD-11: 2C60]
Target Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
 Regulator Info 
Target Regulation Up regulation
Responsed Drug Tamoxifen Approved
 Drug Info 
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Cell Process Cell migration and invasion
In-vitro Model HCC1806 Breast squamous cell carcinoma Homo sapiens CVCL_1258
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
Ovarian cancer [ICD-11: 2C73]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [9]
Response Summary METTL3 knockdown downregulated the phosphorylation levels of RAC-alpha serine/threonine-protein kinase (AKT1) and the expression of the downstream effector Cyclin D1 in ovarian cancer.
Responsed Disease Ovarian cancer [ICD-11: 2C73]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Apoptosis hsa04210
PI3K-Akt signaling pathway hsa04151
Cell Process Cell cycle
Cell apoptosis
In-vitro Model OVCAR-3 Ovarian serous adenocarcinoma Homo sapiens CVCL_0465
SK-OV-3 Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
Prostate cancer [ICD-11: 2C82]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [10]
Response Summary Knock-down of YTHDF2 or METTL3 significantly induced the expression of LHPP and NKX3-1 at both mRNA and protein level with inhibited phosphorylated RAC-alpha serine/threonine-protein kinase (AKT1). YTHDF2 mediates the mRNA degradation of the tumor suppressors LHPP and NKX3-1 in m6A-dependent way to regulate AKT phosphorylation-induced tumor progression in prostate cancer.
Responsed Disease Prostate cancer [ICD-11: 2C82]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Oxidative phosphorylation hsa00190
In-vitro Model VCaP Prostate carcinoma Homo sapiens CVCL_2235
RWPE-1 Normal Homo sapiens CVCL_3791
PC-3 Prostate carcinoma Homo sapiens CVCL_0035
DU145 Prostate carcinoma Homo sapiens CVCL_0105
22Rv1 Prostate carcinoma Homo sapiens CVCL_1045
In-vivo Model Approximately 2 × 106 PCa cells (PC-3 shNC, shYTHDF2, shMETTL3 cell lines) per mouse suspended in 100 uL PBS were injected in the flank of male BALB/c nude mice (4 weeks old). During the 40-day observation, the tumor size (V = (width2×length ×0.52)) was measured with vernier caliper. Approximately 1.5 × 106 PCa cells suspended in 100 uL of PBS (PC-3 shNC, shYTHDF2, and shMETTL3 cell lines) per mouse were injected into the tail vein of male BALB/c nude mice (4 weeks old). The IVIS Spectrum animal imaging system (PerkinElmer) was used to evaluate the tumor growth (40 days) and whole metastasis conditions (4 weeks and 6 weeks) with 100 uL XenoLight D-luciferin Potassium Salt (15 mg/ml, Perkin Elmer) per mouse. Mice were anesthetized and then sacrificed for tumors and metastases which were sent for further organ-localized imaging as above, IHC staining and hematoxylin-eosin (H&E) staining.
Experiment 2 Reporting the m6A-centered Disease Response [10]
Response Summary Knock-down of YTHDF2 or METTL3 significantly induced the expression of LHPP and NKX3-1 at both mRNA and protein level with inhibited phosphorylated RAC-alpha serine/threonine-protein kinase (AKT1). YTHDF2 mediates the mRNA degradation of the tumor suppressors LHPP and NKX3-1 in m6A-dependent way to regulate AKT phosphorylation-induced tumor progression in prostate cancer.
Responsed Disease Prostate cancer [ICD-11: 2C82]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Oxidative phosphorylation hsa00190
In-vitro Model VCaP Prostate carcinoma Homo sapiens CVCL_2235
RWPE-1 Normal Homo sapiens CVCL_3791
PC-3 Prostate carcinoma Homo sapiens CVCL_0035
DU145 Prostate carcinoma Homo sapiens CVCL_0105
22Rv1 Prostate carcinoma Homo sapiens CVCL_1045
Renal cell carcinoma [ICD-11: 2C90]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [11]
Response Summary Knockdown of METTL3 could obviously promote cell proliferation, migration and invasion function, and induce G0/G1 arrest,METTL3 acts as a novel marker for tumorigenesis, development and survival of RCC. Knockdown of METTL3 promoted changes in pI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR markers' expression with a gain in p-PI3k, p-AKT, p-mTOR and p-p70, and a loss of p-4EBP1.
Responsed Disease Renal cell carcinoma [ICD-11: 2C90]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Cell Process Epithelial-to-mesenchymal transition
Arrest cell cycle at G0/G1 phase
In-vitro Model ACHN Papillary renal cell carcinoma Homo sapiens CVCL_1067
Caki-1 Clear cell renal cell carcinoma Homo sapiens CVCL_0234
Caki-2 Papillary renal cell carcinoma Homo sapiens CVCL_0235
HK2 Normal Acipenser baerii CVCL_YE28
In-vivo Model Cells (5×106 cells in 200 uL) were suspended with 100 uL PBS and 100 uL Matrigel Matrix, and injected subcutaneously into the left armpit of each mouse.
Retina cancer [ICD-11: 2D02]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [12]
Response Summary METTL3 promotes the progression of retinoblastoma through PI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR pathways in vitro and in vivo. METTL3 has an impact on the PI3K-AKT-mTOR-P70S6K/4EBP1 pathway. The cell proliferation results show that the stimulatory function of METTL3 is lost after rapamycin treatment.
Responsed Disease Retinoblastoma [ICD-11: 2D02.2]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
mTOR signaling pathway hsa04150
Apoptosis hsa04210
Cell Process Cell proliferation
Cell migration
Cell invasion
Cell apoptosis
In-vitro Model WERI-Rb-1 Retinoblastoma Homo sapiens CVCL_1792
Y-79 Retinoblastoma Homo sapiens CVCL_1893
In-vivo Model To establish a subcutaneous tumour model in nude mice, 2 × 107 Y79 cells (METTL3 knockdown group: shNC, shRNA1 and shRNA2; METTL3 up-regulated group: NC and METLL3) were resuspended in 1 mL of pre-cooled PBS, and 200 uL of the cell suspension was injected subcutaneously into the left side of the armpit to investigate tumour growth (4 × 106 per mouse).
Gangrene or necrosis of lung [ICD-11: CA43]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [17]
Response Summary N6-methyladenosine (m6A) methylation modification is implicated in the pathogenesis of lung ischemia-reperfusion injury. YTHDF3 or IGF2BP2 knockdown inhibited hypoxia/reoxygenation-activated p38, ERK1/2, RAC-alpha serine/threonine-protein kinase (AKT1), and NF-Kappa-B pathways in BEAS-2B cells, and inhibited p-p65, IL-1-beta and TNF-alpha secretion.
Responsed Disease Gangrene or necrosis of lung [ICD-11: CA43]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Apoptosis hsa04210
Cell Process Biological regulation
Cell apoptosis
In-vitro Model BEAS-2B Normal Homo sapiens CVCL_0168
In-vivo Model After being anesthetized with urethane (i.p.), SD rats were endotracheally intubated and ventilated using an animal ventilator under the conditions: respiratory rate of 70 breaths/min, tidal volume of 20 ml/kg, and inspiratory/expiratory ratio of 1:1.
Experiment 2 Reporting the m6A-centered Disease Response [17]
Response Summary N6-methyladenosine (m6A) methylation modification is implicated in the pathogenesis of lung ischemia-reperfusion injury. YTHDF3 or IGF2BP2 knockdown inhibited hypoxia/reoxygenation-activated p38, ERK1/2, RAC-alpha serine/threonine-protein kinase (AKT1), and NF-Kappa-B pathways in BEAS-2B cells, and inhibited p-p65, IL-1-beta and TNF-alpha secretion.
Responsed Disease Gangrene or necrosis of lung [ICD-11: CA43]
Target Regulator YTH domain-containing family protein 3 (YTHDF3) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Apoptosis hsa04210
Cell Process Biological regulation
Cell apoptosis
In-vitro Model BEAS-2B Normal Homo sapiens CVCL_0168
In-vivo Model After being anesthetized with urethane (i.p.), SD rats were endotracheally intubated and ventilated using an animal ventilator under the conditions: respiratory rate of 70 breaths/min, tidal volume of 20 ml/kg, and inspiratory/expiratory ratio of 1:1.
Ossification of spinal ligaments [ICD-11: FA83]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [14]
Response Summary The overexpression of ALKBH5 led to the activation of RAC-alpha serine/threonine-protein kinase (AKT1), and BMP2 was regulated by ALKBH5 through the AKT signaling pathway. ALKBH5 promoted the osteogenesis of the ligamentum flavum cells through BMP2 demethylation and AKT activation. MK22606 is an AKT inhibitor. Moreover, when ALKBH5 was knocked down in the ligamentum flavum cells, p-AKT was inhibited when compared with that in the overexpressed ALKBH5 and control groups.
Responsed Disease Ossification of spinal ligaments [ICD-11: FA83]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
Target Regulation Up regulation
Responsed Drug MK22606 Investigative
 Drug Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Ossification
In-vitro Model Ligamentum flavum cells (Ligamentum flavum cells)
Fulvestrant [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [16]
Response Summary In breast cancer, modest stable overexpression of A2B1 in MCF-7 cells (MCF-7-A2B1 cells) resulted in tamoxifen and fulvestrant- resistance whereas knockdown of A2B1 in LCC9 and LY2 cells restored tamoxifen and fulvestrant, endocrine-sensitivity. MCF-7-A2B1 cells have increased ER-alpha and reduced miR-222-3p that targets ER-alpha. MCF-7-A2B1 have activated RAC-alpha serine/threonine-protein kinase (AKT1) and MAPK that depend on A2B1 expression and are growth inhibited by inhibitors of these pathways.
Target Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
 Regulator Info 
Target Regulation Up regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Cell Process Cell migration and invasion
In-vitro Model HCC1806 Breast squamous cell carcinoma Homo sapiens CVCL_1258
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
Tamoxifen [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [16]
Response Summary In breast cancer, modest stable overexpression of A2B1 in MCF-7 cells (MCF-7-A2B1 cells) resulted in tamoxifen and fulvestrant - resistance whereas knockdown of A2B1 in LCC9 and LY2 cells restored tamoxifen and fulvestrant, endocrine-sensitivity. MCF-7-A2B1 cells have increased ER-alpha and reduced miR-222-3p that targets ER-alpha. MCF-7-A2B1 have activated RAC-alpha serine/threonine-protein kinase (AKT1) and MAPK that depend on A2B1 expression and are growth inhibited by inhibitors of these pathways.
Target Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
 Regulator Info 
Target Regulation Up regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Cell Process Cell migration and invasion
In-vitro Model HCC1806 Breast squamous cell carcinoma Homo sapiens CVCL_1258
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
MK22606 [Investigative]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [14]
Response Summary The overexpression of ALKBH5 led to the activation of RAC-alpha serine/threonine-protein kinase (AKT1), and BMP2 was regulated by ALKBH5 through the AKT signaling pathway. ALKBH5 promoted the osteogenesis of the ligamentum flavum cells through BMP2 demethylation and AKT activation. MK22606 is an AKT inhibitor. Moreover, when ALKBH5 was knocked down in the ligamentum flavum cells, p-AKT was inhibited when compared with that in the overexpressed ALKBH5 and control groups.
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
Target Regulation Up regulation
Responsed Disease Ossification of spinal ligaments ICD-11: FA83
 Disease Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Ossification
In-vitro Model Ligamentum flavum cells (Ligamentum flavum cells)
References
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