m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00222)
Target Name Catenin beta-1 (CTNNB1/Beta-catenin)
Synonyms
Beta-catenin; CTNNB; OK/SW-cl.35; PRO2286
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Gene Name CTNNB1
Chromosomal Location 3p22.1
Family beta-catenin family
Function
Key downstream component of the canonical Wnt signaling pathway. In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes. Involved in the regulation of cell adhesion, as component of an E-cadherin:catenin adhesion complex (By similarity). Acts as a negative regulator of centrosome cohesion. Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization. Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2. Disrupts PML function and PML-NB formation by inhibiting RANBP2-mediated sumoylation of PML. Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle (By similarity). Involved in chondrocyte differentiation via interaction with SOX9: SOX9-binding competes with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling (By similarity).
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Gene ID 1499
Uniprot ID
CTNB1_HUMAN
HGNC ID
HGNC:2514
Ensembl Gene ID
ENSG00000168036
KEGG ID
hsa:1499
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
CTNNB1 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 3 (METTL3) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line Embryonic stem cells Mus musculus
Treatment: METTL3 knockout mESCs
Control: Wild type mESCs
 GSE156481
Regulation
logFC: -8.46E-01
p-value: 2.97E-40
More Results Click to View More RNA-seq Results
Representative RIP-seq result supporting the interaction between CTNNB1 and the regulator
Cell Line MDA-MB-231 Homo sapiens
Regulation logFC: 1.37E+00 GSE60213
In total 3 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary METTL3 activated the luciferase activity of TOPflash (a reporter for beta-catenin/TCF signaling), and downregulation of METTL3 inhibited the expression of Catenin beta-1 (CTNNB1/Beta-catenin)/TCF target genes vimentin and N-cadherin, which are two regulators of epithelial-mesenchymal transition. METTL3 silencing decreased the m6A methylation and total mRNA levels of Tankyrase, a negative regulator of axin. METTL3 is a therapeutic target for NPC.
Target Regulation Up regulation
Responsed Disease Nasopharyngeal carcinoma ICD-11: 2B6B
 Disease Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process Epithelial-mesenchymal transition
In-vitro Model Neural progenitor cells (NPCs) (The progenitor cells of the CNS)
NP69 (A human immortalized nasopharyngeal epithelial)
HNE-2 Nasopharyngeal carcinoma Homo sapiens CVCL_FA07
HNE-1 Nasopharyngeal carcinoma Homo sapiens CVCL_0308
CNE-2 Nasopharyngeal carcinoma Homo sapiens CVCL_6889
CNE-1 Normal Homo sapiens CVCL_6888
In-vivo Model 1 × 105 HNE2 cells (with or without METTL3 knockdown) were labeled with luciferase gene and injected into the tail vein of the nude mice.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary METTL3 is significantly up-regulated in Hepatoblastoma(HB) and promotes HB development.m6A mRNA methylation contributes significantly to regulate the Wnt/beta-catenin pathway. Reduced m6A methylation can lead to a decrease in expression and stability of the Catenin beta-1 (CTNNB1/Beta-catenin).
Target Regulation Up regulation
Responsed Disease Hepatoblastoma ICD-11: 2C12.01
 Disease Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process RNA stability
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
L-02 Endocervical adenocarcinoma Homo sapiens CVCL_6926
QSG-7701 Endocervical adenocarcinoma Homo sapiens CVCL_6944
In-vivo Model 5 × 106 cells were subcutaneously injected into the left or right flank of each mouse.
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary SAM not only played a compensatory role, but also led to m6A modification changes in neural tube development and regulation. Ethionine affected m6A modification by reducing SAM metabolism. METTL3 is enriched in HT-22 cells, and METTL3 knockdown reduces cell proliferation and increases apoptosis through suppressing Wnt/Catenin beta-1 (CTNNB1/Beta-catenin) signaling pathway. Overexpression of ALKBH5 can only inhibit cell proliferation, but cannot promote cell apoptosis.
Target Regulation Down regulation
Responsed Disease Neural tube defect ICD-11: LA02.Z
 Disease Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process Cell apoptosis
In-vitro Model HT22 Normal Mus musculus CVCL_0321
In-vivo Model The mice were maintained on a 12-h light/dark cycle (lights on from 8:00 a.m. to 8:00 p.m.). On day 7.5 of pregnancy (E7.5), ethionine (Sigma-Aldrich, USA) was intraperitoneally injected only once at a dose of 500 mg/kg to establish the NTDs embryo model. And SAM (MedChemExpress, USA) was intraperitoneally injected only once at a dose of 30 mg/kg. The same dose was intraperitoneally injected to the pregnant mice for control group.
Methyltransferase-like 14 (METTL14) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL14
Cell Line BMDM Mus musculus
Treatment: METTL14 knockout mice BMDM
Control: Wild type mice BMDM
 GSE153512
Regulation
logFC: -6.10E-01
p-value: 2.52E-16
More Results Click to View More RNA-seq Results
In total 4 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [4]
Response Summary m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Target Regulation Down regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Drug Pertuzumab Approved
 Drug Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process Glutathione synthesis
In-vitro Model ZR-75-1 Invasive breast carcinoma Homo sapiens CVCL_0588
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
SUM-159 (A mesenchymal triple-negative breast cancer cell line)
SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
MDA-MB-361 Breast adenocarcinoma Homo sapiens CVCL_0620
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF-10A Normal Homo sapiens CVCL_0598
HEK293T Normal Homo sapiens CVCL_0063
BT-549 Invasive breast carcinoma Homo sapiens CVCL_1092
BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
AU565 Breast adenocarcinoma Homo sapiens CVCL_1074
In-vivo Model Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 107 cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [4]
Response Summary m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Target Regulation Down regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Drug Trastuzumab Approved
 Drug Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process Glutathione synthesis
In-vitro Model ZR-75-1 Invasive breast carcinoma Homo sapiens CVCL_0588
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
SUM-159 (A mesenchymal triple-negative breast cancer cell line)
SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
MDA-MB-361 Breast adenocarcinoma Homo sapiens CVCL_0620
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF-10A Normal Homo sapiens CVCL_0598
HEK293T Normal Homo sapiens CVCL_0063
BT-549 Invasive breast carcinoma Homo sapiens CVCL_1092
BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
AU565 Breast adenocarcinoma Homo sapiens CVCL_1074
In-vivo Model Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 107 cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [4]
Response Summary m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Target Regulation Down regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Drug Tucatinib Approved
 Drug Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process Glutathione synthesis
In-vitro Model ZR-75-1 Invasive breast carcinoma Homo sapiens CVCL_0588
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
SUM-159 (A mesenchymal triple-negative breast cancer cell line)
SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
MDA-MB-361 Breast adenocarcinoma Homo sapiens CVCL_0620
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF-10A Normal Homo sapiens CVCL_0598
HEK293T Normal Homo sapiens CVCL_0063
BT-549 Invasive breast carcinoma Homo sapiens CVCL_1092
BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
AU565 Breast adenocarcinoma Homo sapiens CVCL_1074
In-vivo Model Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 107 cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Experiment 4 Reporting the m6A Methylation Regulator of This Target Gene [5]
Response Summary Mettl14 resulted in enhanced levels of Wnt1 m6A modification and Wnt1 protein but not its transcript level.Furthermore, Mettl14 overexpression blocked I/R-induced downregulation of Wnt1 and Catenin beta-1 (CTNNB1/Beta-catenin) proteins, whereas Mettl14 hearts exhibited the opposite results. Mettl14 attenuates cardiac I/R injury by activating Wnt/Bete-catenin in an m6A-dependent manner, providing a novel therapeutic target for ischemic heart disease.
Target Regulation Up regulation
Responsed Disease Ischemic heart disease ICD-11: BA40-BA6Z
 Disease Info 
Pathway Response Wnt signaling pathway hsa04310
In-vitro Model Neonatal rat ventricular cardiomyocytes (Primary myocyte cells)
In-vivo Model C57BL/6 mouse hearts were subjected to ischemia/reperfusion (I/R) in vivo as described previously (Bock-Marquette et al., 2004; Song et al., 2015; Brocard et al., 2017). I/R injury in mice was induced by 45-min ischemia, followed by 7-day and 4-week reperfusion in a loss-of-function study (Figure 1) and gain-of-function study (Figure 2), respectively. In brief, mice were anesthetized with 2% avertin (0.1 ml/10g body weight; Sigma-Aldrich Corporation, United States) through intraperitoneal injection. To generate I/R injury, the left anterior descending coronary artery (LAD) was ligated with 7-0 nylon for 45 min and then was removed. For the sham group, a suture was passed under the LAD but without ligation. According to the experimental requirements, at different time points of cardiac I/R, the mice were anesthetized for assessing heart function by echocardiographic measurement. All the mice survived during the process of I/R injury after the operation.
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: -1.63E+00
p-value: 8.42E-15
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary SAM not only played a compensatory role, but also led to m6A modification changes in neural tube development and regulation. Ethionine affected m6A modification by reducing SAM metabolism. METTL3 is enriched in HT-22 cells, and METTL3 knockdown reduces cell proliferation and increases apoptosis through suppressing Wnt/Catenin beta-1 (CTNNB1/Beta-catenin) signaling pathway. Overexpression of ALKBH5 can only inhibit cell proliferation, but cannot promote cell apoptosis.
Responsed Disease Neural tube defect ICD-11: LA02.Z
 Disease Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process Cell apoptosis
In-vitro Model HT22 Normal Mus musculus CVCL_0321
In-vivo Model The mice were maintained on a 12-h light/dark cycle (lights on from 8:00 a.m. to 8:00 p.m.). On day 7.5 of pregnancy (E7.5), ethionine (Sigma-Aldrich, USA) was intraperitoneally injected only once at a dose of 500 mg/kg to establish the NTDs embryo model. And SAM (MedChemExpress, USA) was intraperitoneally injected only once at a dose of 30 mg/kg. The same dose was intraperitoneally injected to the pregnant mice for control group.
YTH domain-containing family protein 1 (YTHDF1) [READER]
 Regulator Info 
Representative RIP-seq result supporting the interaction between CTNNB1 and the regulator
Cell Line Hela Homo sapiens
Regulation logFC: 2.05E+00 GSE63591
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [6]
Response Summary Silencing YTHDF1 significantly inhibited Wnt/Catenin beta-1 (CTNNB1/Beta-catenin) pathway activity in Colorectal cancer cells.
Target Regulation Up regulation
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Pathway Response Wnt signaling pathway hsa04310
Signaling pathways regulating pluripotency of stem cells hsa04550
Cell Process Cell Tumorigenicity
In-vitro Model NCM460 Normal Homo sapiens CVCL_0460
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
SW620 Colon adenocarcinoma Homo sapiens CVCL_0547
In-vivo Model 1 × 105 parental HT29-shNC cells, HT29-shYTHDF1 cells, HT29-shNC colonospheres, and HT29-shYTHDF1 colonospheres were inoculated subcutaneously into the left inguinal folds of the nude mice.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [7]
Response Summary ECs transmitted miR-376c into NSCLC cells through Evs, and inhibited the intracellular YTHDF1 expression and the Wnt/Catenin beta-1 (CTNNB1/Beta-catenin) pathway activation. YTHDF1 overexpression reversed the inhibitory role of miR-376c released by EC-Evs in non-small cell lung cancer cells.
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Cell Process Cell proliferation
Cell invasion
Cell migration
Cell apoptosis
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-1650 (Non-Small Cell Lung Cancer Cells)
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H358 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
YTH domain-containing family protein 3 (YTHDF3) [READER]
 Regulator Info 
Representative RIP-seq result supporting the interaction between CTNNB1 and the regulator
Cell Line Hela Homo sapiens
Regulation logFC: 1.43E+00 GSE86214
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [8]
Response Summary YTHDF3 enhances Catenin beta-1 (CTNNB1/Beta-catenin) translation through recognizing and binding the m6A peaks on CTNNB1 mRNA.m6A reading protein YTHDF3 promotes the translation of the target transcript CTNNB1, contributing to ocular melanoma propagation and migration through m6A methylation.
Target Regulation Up regulation
Responsed Disease Melanoma of uvea ICD-11: 2D0Y
 Disease Info 
Fat mass and obesity-associated protein (FTO) [ERASER]
 Regulator Info 
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [9]
Response Summary FTO expression was significantly upregulated in HNSCC datasets and tissues. FTO expression was significantly correlated with Catenin beta-1 (CTNNB1/Beta-catenin) expression. Moreover, it exerted a tumorigenic effect by increasing CTNNB1 expression in an m6A-dependent manner.
Target Regulation Up regulation
Responsed Disease Head and neck squamous carcinoma ICD-11: 2B6E
 Disease Info 
Pathway Response Adherens junction hsa04520
Cell Process Cell proliferation and migration
In-vitro Model CAL-27 Tongue squamous cell carcinoma Homo sapiens CVCL_1107
FaDu Hypopharyngeal squamous cell carcinoma Homo sapiens CVCL_1218
Tu 686 Laryngeal squamous cell carcinoma Homo sapiens CVCL_4916
HN-6 Tongue squamous cell carcinoma Homo sapiens CVCL_8129
HEp-2 Endocervical adenocarcinoma Homo sapiens CVCL_1906
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [10]
Response Summary The mRNA level of FTO is elevated in cervical squamous cell carcinoma (CSCC) tissues when compared with respective adjacent normal tissues.FTO enhances the chemo-radiotherapy resistance both in vitro and in vivo through regulating expression of Catenin beta-1 (CTNNB1/Beta-catenin) by reducing m6A levels in its mRNA transcripts and in turn increases excision repair cross-complementation group 1 (ERCC1) activity.
Target Regulation Up regulation
Responsed Disease Cervical squamous cell carcinoma ICD-11: 2E66.2
 Disease Info 
Cell Process RNA decay
In-vitro Model C-33 A Cervical squamous cell carcinoma Homo sapiens CVCL_1094
SiHa Cervical squamous cell carcinoma Homo sapiens CVCL_0032
In-vivo Model Either SiHa cells or FTO overexpressed SiHa cells were injected subcutaneously into the right flanks of 4- to 6-week-old female athymic nude mice (CAS, Beijing, China). The mice were divided into four groups (N = 6). After transplantation, tumor size was measured by caliper every other day. Tumor volume was calculated using the formula: volume = (length × width2)/2. When the tumor volumes reached 50 mm3, the animals were treated with intraperitoneal injection of cisplatin (3 mg/kg) every other day for seven times and local irradiation of 8 Gy one time.
Nasopharyngeal carcinoma [ICD-11: 2B6B]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary METTL3 activated the luciferase activity of TOPflash (a reporter for beta-catenin/TCF signaling), and downregulation of METTL3 inhibited the expression of Catenin beta-1 (CTNNB1/Beta-catenin)/TCF target genes vimentin and N-cadherin, which are two regulators of epithelial-mesenchymal transition. METTL3 silencing decreased the m6A methylation and total mRNA levels of Tankyrase, a negative regulator of axin. METTL3 is a therapeutic target for NPC.
Responsed Disease Nasopharyngeal carcinoma [ICD-11: 2B6B]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Wnt signaling pathway hsa04310
Cell Process Epithelial-mesenchymal transition
In-vitro Model Neural progenitor cells (NPCs) (The progenitor cells of the CNS)
NP69 (A human immortalized nasopharyngeal epithelial)
HNE-2 Nasopharyngeal carcinoma Homo sapiens CVCL_FA07
HNE-1 Nasopharyngeal carcinoma Homo sapiens CVCL_0308
CNE-2 Nasopharyngeal carcinoma Homo sapiens CVCL_6889
CNE-1 Normal Homo sapiens CVCL_6888
In-vivo Model 1 × 105 HNE2 cells (with or without METTL3 knockdown) were labeled with luciferase gene and injected into the tail vein of the nude mice.
Head and neck squamous carcinoma [ICD-11: 2B6E]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [9]
Response Summary FTO expression was significantly upregulated in HNSCC datasets and tissues. FTO expression was significantly correlated with Catenin beta-1 (CTNNB1/Beta-catenin) expression. Moreover, it exerted a tumorigenic effect by increasing CTNNB1 expression in an m6A-dependent manner.
Responsed Disease Head and neck squamous carcinoma [ICD-11: 2B6E]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Adherens junction hsa04520
Cell Process Cell proliferation and migration
In-vitro Model CAL-27 Tongue squamous cell carcinoma Homo sapiens CVCL_1107
FaDu Hypopharyngeal squamous cell carcinoma Homo sapiens CVCL_1218
Tu 686 Laryngeal squamous cell carcinoma Homo sapiens CVCL_4916
HN-6 Tongue squamous cell carcinoma Homo sapiens CVCL_8129
HEp-2 Endocervical adenocarcinoma Homo sapiens CVCL_1906
Colorectal cancer [ICD-11: 2B91]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [6]
Response Summary Silencing YTHDF1 significantly inhibited Wnt/Catenin beta-1 (CTNNB1/Beta-catenin) pathway activity in Colorectal cancer cells.
Responsed Disease Colorectal cancer [ICD-11: 2B91]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Wnt signaling pathway hsa04310
Signaling pathways regulating pluripotency of stem cells hsa04550
Cell Process Cell Tumorigenicity
In-vitro Model NCM460 Normal Homo sapiens CVCL_0460
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
SW620 Colon adenocarcinoma Homo sapiens CVCL_0547
In-vivo Model 1 × 105 parental HT29-shNC cells, HT29-shYTHDF1 cells, HT29-shNC colonospheres, and HT29-shYTHDF1 colonospheres were inoculated subcutaneously into the left inguinal folds of the nude mice.
Liver cancer [ICD-11: 2C12]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary METTL3 is significantly up-regulated in Hepatoblastoma(HB) and promotes HB development.m6A mRNA methylation contributes significantly to regulate the Wnt/beta-catenin pathway. Reduced m6A methylation can lead to a decrease in expression and stability of the Catenin beta-1 (CTNNB1/Beta-catenin).
Responsed Disease Hepatoblastoma [ICD-11: 2C12.01]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Wnt signaling pathway hsa04310
Cell Process RNA stability
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
L-02 Endocervical adenocarcinoma Homo sapiens CVCL_6926
QSG-7701 Endocervical adenocarcinoma Homo sapiens CVCL_6944
In-vivo Model 5 × 106 cells were subcutaneously injected into the left or right flank of each mouse.
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [7]
Response Summary ECs transmitted miR-376c into NSCLC cells through Evs, and inhibited the intracellular YTHDF1 expression and the Wnt/Catenin beta-1 (CTNNB1/Beta-catenin) pathway activation. YTHDF1 overexpression reversed the inhibitory role of miR-376c released by EC-Evs in non-small cell lung cancer cells.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Cell Process Cell proliferation
Cell invasion
Cell migration
Cell apoptosis
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-1650 (Non-Small Cell Lung Cancer Cells)
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H358 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
Melanoma [ICD-11: 2C30]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [8]
Response Summary YTHDF3 enhances Catenin beta-1 (CTNNB1/Beta-catenin) translation through recognizing and binding the m6A peaks on CTNNB1 mRNA.m6A reading protein YTHDF3 promotes the translation of the target transcript CTNNB1, contributing to ocular melanoma propagation and migration through m6A methylation.
Responsed Disease Melanoma of uvea [ICD-11: 2D0Y]
Target Regulator YTH domain-containing family protein 3 (YTHDF3) READER
 Regulator Info 
Target Regulation Up regulation
Breast cancer [ICD-11: 2C60]
 Disease Info 
In total 3 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [4]
Response Summary m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Responsed Disease Breast cancer [ICD-11: 2C60]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Responsed Drug Pertuzumab Approved
 Drug Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process Glutathione synthesis
In-vitro Model ZR-75-1 Invasive breast carcinoma Homo sapiens CVCL_0588
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
SUM-159 (A mesenchymal triple-negative breast cancer cell line)
SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
MDA-MB-361 Breast adenocarcinoma Homo sapiens CVCL_0620
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF-10A Normal Homo sapiens CVCL_0598
HEK293T Normal Homo sapiens CVCL_0063
BT-549 Invasive breast carcinoma Homo sapiens CVCL_1092
BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
AU565 Breast adenocarcinoma Homo sapiens CVCL_1074
In-vivo Model Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 107 cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Experiment 2 Reporting the m6A-centered Disease Response [4]
Response Summary m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Responsed Disease Breast cancer [ICD-11: 2C60]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Responsed Drug Trastuzumab Approved
 Drug Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process Glutathione synthesis
In-vitro Model ZR-75-1 Invasive breast carcinoma Homo sapiens CVCL_0588
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
SUM-159 (A mesenchymal triple-negative breast cancer cell line)
SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
MDA-MB-361 Breast adenocarcinoma Homo sapiens CVCL_0620
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF-10A Normal Homo sapiens CVCL_0598
HEK293T Normal Homo sapiens CVCL_0063
BT-549 Invasive breast carcinoma Homo sapiens CVCL_1092
BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
AU565 Breast adenocarcinoma Homo sapiens CVCL_1074
In-vivo Model Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 107 cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Experiment 3 Reporting the m6A-centered Disease Response [4]
Response Summary m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Responsed Disease Breast cancer [ICD-11: 2C60]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Responsed Drug Tucatinib Approved
 Drug Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process Glutathione synthesis
In-vitro Model ZR-75-1 Invasive breast carcinoma Homo sapiens CVCL_0588
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
SUM-159 (A mesenchymal triple-negative breast cancer cell line)
SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
MDA-MB-361 Breast adenocarcinoma Homo sapiens CVCL_0620
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF-10A Normal Homo sapiens CVCL_0598
HEK293T Normal Homo sapiens CVCL_0063
BT-549 Invasive breast carcinoma Homo sapiens CVCL_1092
BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
AU565 Breast adenocarcinoma Homo sapiens CVCL_1074
In-vivo Model Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 107 cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Cervical intraepithelial neoplasia [ICD-11: 2E66]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [10]
Response Summary The mRNA level of FTO is elevated in cervical squamous cell carcinoma (CSCC) tissues when compared with respective adjacent normal tissues.FTO enhances the chemo-radiotherapy resistance both in vitro and in vivo through regulating expression of Catenin beta-1 (CTNNB1/Beta-catenin) by reducing m6A levels in its mRNA transcripts and in turn increases excision repair cross-complementation group 1 (ERCC1) activity.
Responsed Disease Cervical squamous cell carcinoma [ICD-11: 2E66.2]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Up regulation
Cell Process RNA decay
In-vitro Model C-33 A Cervical squamous cell carcinoma Homo sapiens CVCL_1094
SiHa Cervical squamous cell carcinoma Homo sapiens CVCL_0032
In-vivo Model Either SiHa cells or FTO overexpressed SiHa cells were injected subcutaneously into the right flanks of 4- to 6-week-old female athymic nude mice (CAS, Beijing, China). The mice were divided into four groups (N = 6). After transplantation, tumor size was measured by caliper every other day. Tumor volume was calculated using the formula: volume = (length × width2)/2. When the tumor volumes reached 50 mm3, the animals were treated with intraperitoneal injection of cisplatin (3 mg/kg) every other day for seven times and local irradiation of 8 Gy one time.
Ischemic heart disease [ICD-11: BA40-BA6Z]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [5]
Response Summary Mettl14 resulted in enhanced levels of Wnt1 m6A modification and Wnt1 protein but not its transcript level.Furthermore, Mettl14 overexpression blocked I/R-induced downregulation of Wnt1 and Catenin beta-1 (CTNNB1/Beta-catenin) proteins, whereas Mettl14 hearts exhibited the opposite results. Mettl14 attenuates cardiac I/R injury by activating Wnt/Bete-catenin in an m6A-dependent manner, providing a novel therapeutic target for ischemic heart disease.
Responsed Disease Ischemic heart disease [ICD-11: BA40-BA6Z]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Wnt signaling pathway hsa04310
In-vitro Model Neonatal rat ventricular cardiomyocytes (Primary myocyte cells)
In-vivo Model C57BL/6 mouse hearts were subjected to ischemia/reperfusion (I/R) in vivo as described previously (Bock-Marquette et al., 2004; Song et al., 2015; Brocard et al., 2017). I/R injury in mice was induced by 45-min ischemia, followed by 7-day and 4-week reperfusion in a loss-of-function study (Figure 1) and gain-of-function study (Figure 2), respectively. In brief, mice were anesthetized with 2% avertin (0.1 ml/10g body weight; Sigma-Aldrich Corporation, United States) through intraperitoneal injection. To generate I/R injury, the left anterior descending coronary artery (LAD) was ligated with 7-0 nylon for 45 min and then was removed. For the sham group, a suture was passed under the LAD but without ligation. According to the experimental requirements, at different time points of cardiac I/R, the mice were anesthetized for assessing heart function by echocardiographic measurement. All the mice survived during the process of I/R injury after the operation.
Spina bifida [ICD-11: LA02]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary SAM not only played a compensatory role, but also led to m6A modification changes in neural tube development and regulation. Ethionine affected m6A modification by reducing SAM metabolism. METTL3 is enriched in HT-22 cells, and METTL3 knockdown reduces cell proliferation and increases apoptosis through suppressing Wnt/Catenin beta-1 (CTNNB1/Beta-catenin) signaling pathway. Overexpression of ALKBH5 can only inhibit cell proliferation, but cannot promote cell apoptosis.
Responsed Disease Neural tube defect [ICD-11: LA02.Z]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response Wnt signaling pathway hsa04310
Cell Process Cell apoptosis
In-vitro Model HT22 Normal Mus musculus CVCL_0321
In-vivo Model The mice were maintained on a 12-h light/dark cycle (lights on from 8:00 a.m. to 8:00 p.m.). On day 7.5 of pregnancy (E7.5), ethionine (Sigma-Aldrich, USA) was intraperitoneally injected only once at a dose of 500 mg/kg to establish the NTDs embryo model. And SAM (MedChemExpress, USA) was intraperitoneally injected only once at a dose of 30 mg/kg. The same dose was intraperitoneally injected to the pregnant mice for control group.
Experiment 2 Reporting the m6A-centered Disease Response [3]
Response Summary SAM not only played a compensatory role, but also led to m6A modification changes in neural tube development and regulation. Ethionine affected m6A modification by reducing SAM metabolism. METTL3 is enriched in HT-22 cells, and METTL3 knockdown reduces cell proliferation and increases apoptosis through suppressing Wnt/Catenin beta-1 (CTNNB1/Beta-catenin) signaling pathway. Overexpression of ALKBH5 can only inhibit cell proliferation, but cannot promote cell apoptosis.
Responsed Disease Neural tube defect [ICD-11: LA02.Z]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process Cell apoptosis
In-vitro Model HT22 Normal Mus musculus CVCL_0321
In-vivo Model The mice were maintained on a 12-h light/dark cycle (lights on from 8:00 a.m. to 8:00 p.m.). On day 7.5 of pregnancy (E7.5), ethionine (Sigma-Aldrich, USA) was intraperitoneally injected only once at a dose of 500 mg/kg to establish the NTDs embryo model. And SAM (MedChemExpress, USA) was intraperitoneally injected only once at a dose of 30 mg/kg. The same dose was intraperitoneally injected to the pregnant mice for control group.
Pertuzumab [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [4]
Response Summary m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process Glutathione synthesis
In-vitro Model ZR-75-1 Invasive breast carcinoma Homo sapiens CVCL_0588
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
SUM-159 (A mesenchymal triple-negative breast cancer cell line)
SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
MDA-MB-361 Breast adenocarcinoma Homo sapiens CVCL_0620
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF-10A Normal Homo sapiens CVCL_0598
HEK293T Normal Homo sapiens CVCL_0063
BT-549 Invasive breast carcinoma Homo sapiens CVCL_1092
BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
AU565 Breast adenocarcinoma Homo sapiens CVCL_1074
In-vivo Model Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 107 cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Trastuzumab [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [4]
Response Summary m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process Glutathione synthesis
In-vitro Model ZR-75-1 Invasive breast carcinoma Homo sapiens CVCL_0588
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
SUM-159 (A mesenchymal triple-negative breast cancer cell line)
SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
MDA-MB-361 Breast adenocarcinoma Homo sapiens CVCL_0620
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF-10A Normal Homo sapiens CVCL_0598
HEK293T Normal Homo sapiens CVCL_0063
BT-549 Invasive breast carcinoma Homo sapiens CVCL_1092
BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
AU565 Breast adenocarcinoma Homo sapiens CVCL_1074
In-vivo Model Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 107 cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Tucatinib [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [4]
Response Summary m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process Glutathione synthesis
In-vitro Model ZR-75-1 Invasive breast carcinoma Homo sapiens CVCL_0588
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
SUM-159 (A mesenchymal triple-negative breast cancer cell line)
SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
MDA-MB-361 Breast adenocarcinoma Homo sapiens CVCL_0620
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF-10A Normal Homo sapiens CVCL_0598
HEK293T Normal Homo sapiens CVCL_0063
BT-549 Invasive breast carcinoma Homo sapiens CVCL_1092
BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
AU565 Breast adenocarcinoma Homo sapiens CVCL_1074
In-vivo Model Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 107 cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
References
Ref 1 Upregulated METTL3 in nasopharyngeal carcinoma enhances the motility of cancer cells. Kaohsiung J Med Sci. 2020 Nov;36(11):895-903. doi: 10.1002/kjm2.12266. Epub 2020 Jul 15.
Ref 2 m(6)A mRNA methylation regulates CTNNB1 to promote the proliferation of hepatoblastoma. Mol Cancer. 2019 Dec 23;18(1):188. doi: 10.1186/s12943-019-1119-7.
Ref 3 Ethionine-mediated reduction of S-adenosylmethionine is responsible for the neural tube defects in the developing mouse embryo-mediated m6A modification and is involved in neural tube defects via modulating Wnt/Beta-catenin signaling pathway. Epigenetics Chromatin. 2021 Dec 4;14(1):52. doi: 10.1186/s13072-021-00426-3.
Ref 4 N6-methyladenosine regulated FGFR4 attenuates ferroptotic cell death in recalcitrant HER2-positive breast cancer. Nat Commun. 2022 May 13;13(1):2672. doi: 10.1038/s41467-022-30217-7.
Ref 5 Mettl14 Attenuates Cardiac Ischemia/Reperfusion Injury by Regulating Wnt1/Beta-Catenin Signaling Pathway. Front Cell Dev Biol. 2021 Dec 16;9:762853. doi: 10.3389/fcell.2021.762853. eCollection 2021.
Ref 6 YTHDF1 Regulates Tumorigenicity and Cancer Stem Cell-Like Activity in Human Colorectal Carcinoma. Front Oncol. 2019 May 3;9:332. doi: 10.3389/fonc.2019.00332. eCollection 2019.
Ref 7 Loading MicroRNA-376c in Extracellular Vesicles Inhibits Properties of Non-Small Cell Lung Cancer Cells by Targeting YTHDF1. Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820977525. doi: 10.1177/1533033820977525.
Ref 8 The m(6)A reading protein YTHDF3 potentiates tumorigenicity of cancer stem-like cells in ocular melanoma through facilitating CTNNB1 translation. Oncogene. 2022 Feb;41(9):1281-1297. doi: 10.1038/s41388-021-02146-0. Epub 2022 Feb 3.
Ref 9 The RNA N6-Methyladenosine Demethylase FTO Promotes Head and Neck Squamous Cell Carcinoma Proliferation and Migration by Increasing CTNNB1. Int J Gen Med. 2021 Nov 24;14:8785-8795. doi: 10.2147/IJGM.S339095. eCollection 2021.
Ref 10 FTO regulates the chemo-radiotherapy resistance of cervical squamous cell carcinoma (CSCC) by targeting Beta-catenin through mRNA demethylation. Mol Carcinog. 2018 May;57(5):590-597. doi: 10.1002/mc.22782. Epub 2018 Feb 1.