Name	Breast cancer
ICD	ICD-11: 2C60

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	Adenylate kinase 4 modulates the resistance of breast cancer cells to tamoxifen through an m6A-based epitranscriptomic mechanism. Genetic depletion of METTL3 in TamR MCF-7 cells led to a diminished Adenylate kinase 4, mitochondrial (AK4) protein level and attenuated resistance to tamoxifen.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Tamoxifen		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Mitochondrial apoptosis
In-vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF7-TamR	Invasive breast carcinoma	Homo sapiens	CVCL_EG55

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	FTO up-regulated ADP-ribosylation factor-like protein 5B (ARL5B) by inhibiting miR-181b-3p. The carcinogenic activity of FTO in promoting the invasion and migration of breast cancer cells via the FTO/miR-181b-3p/ARL5B signaling pathway.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell invasion and migration
In-vitro Model	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	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
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	The stabilization of WTAP further promotes RNA m6A methylation of Alpha-enolase (ENO1), impacting the glycolytic activity of BC cells.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Wilms tumor 1-associating protein (WTAP)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glycolysis
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	A total of 1 × 106 luciferase-labeled BC cells transfected with shWTAP or shNC were injected subcutaneously with or without C5aR1 neutrophils (tumor cells:neutrophils, 10:1).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	METTL3 can regulate the expression of MALAT1 through m6A, mediate the E2F1/Anterior gradient protein 2 homolog (AGR2) axis, and promote the adriamycin resistance of breast cancer.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	MCF7-DoxR (Adriamycin-resistant cell line MCF7-DoxR)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
In-vivo Model	Once the tumor volume increased to about 1 cm3, six groups of MCF7 bearing mice (n = 10 in each group) were injected with PBS (0.1 ml, caudal vein) and adriamycin (0.1 ml, 10 mg/kg), respectively. When the tumor reached 1.5 cm in any direction (defined as event-free survival analysis), 10 mice in each group were selected to measure the tumor size and weight on the 12th day after adriamycin injection.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	Apoptosis regulator Bcl-2 (BCL2) acted as the target of METTL3, thereby regulating the proliferation and apoptosis of breast cancer.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell apoptosis
In-vitro Model	MCF-10A	Normal	Homo sapiens	CVCL_0598
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
In-vivo Model	Mice were maintained at 22 ± 2 ℃ with a humidity of 35 ± 5% under a 12 h light and 12 h dark cycle, with free access to water and food. For the HFD experiment, female control (Ftoflox/flox) and adipose-selective fto knockout (Fabp4-Cre Ftoflox/flox, fto-AKO) mice were fed with high-fat diet (60% fat in calories; Research Diets, D12492) for the desired periods of time, and food intake and body weight were measured every week after weaning (at 3 weeks of age).
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	Studies of the aberrant expression of m6A mediators in breast cancer revealed that they were associated with different BC subtypes and functions, such as proliferation, apoptosis, stemness, the cell cycle, migration, and metastasis, through several factors and signaling pathways, such as Apoptosis regulator Bcl-2 (BCL2) and the PI3K/Akt pathway, among others. Fat mass and obesity-associated protein (FTO) was identified as the first m6A demethylase, and a series of inhibitors that target FTO were reported to have potential for the treatment of BC by inhibiting cell proliferation and promoting apoptosis.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Pathway Response	Apoptosis			hsa04210
	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation
	Cell apoptosis

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	METTL3 promotes adriamycin resistance in MCF-7 breast cancer cells by accelerating pri-microRNA-221-3p maturation in a m6A-dependent manner. METTL3 knockdown was shown to reduce the expression of miR-221-3p by reducing pri-miR-221-3p m6A mRNA methylation, reducing the expression of ATP-dependent translocase ABCB1 (ABCB1) and BCRP, and inducing apoptosis. Identified the METTL3/miR-221-3p/HIPK2/Che-1 axis as a novel signaling event that will be responsible for resistance of BC cells to ADR.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell growth and death
	Cell apoptosis
In-vitro Model	ADR-resistant MCF-7 (MCF-7/ADR) cells (Human breast cancer doxorubicin-resistant cell line)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
In-vivo Model	Cell suspensions (2 × 106 cells/mL) made with MCF-7/ADR cells stably expressing METTL3 and/or miR-221-3p inhibitor were subcutaneously implanted into each mouse. One week later, xenografted mice were injected with 0.1 mL ADR (25 mg/kg, intraperitoneal injection) twice a week.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	FTO mediated m6A demethylation in the 3'UTR of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) mRNA and induced its degradation via an YTHDF2 independent mechanism. FTO serves as a novel potential therapeutic target for breast cancer.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell colony formation
	Cell metastasis
In-vitro Model	4 T1 (Mouse breast cancer cells)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
In-vivo Model	For the subcutaneous implantation model, 5 4-week-old female Balb/c mice were randomly grouped and injected with 1 × 106 shCtrl, shFTO or shFTO/shBNIP3 KD 4 T1 cells. For tumor metastasis mouse model, 5 4-week-old female Balb/c mice were randomly grouped and injected with 1 × 106 shCtrl, shFTO or shFTO/shBNIP3 KD 4 T1 cells via tail vein. For orthotopic xenograft mouse model, 5 4-week-old female NOD/SCID mice were randomly grouped.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[9]
Response Summary	ALKBH5 removed the m6A methylation of Breast cancer type 1 susceptibility protein (BRCA1) for mRNA stabilization and further enhanced DNA repair competency to decrease doxorubicin efficacy in breast cancer cells.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	HCC1937	Breast ductal carcinoma	Homo sapiens	CVCL_0290
In-vivo Model	For the subcutaneously transplanted tumor model, wild-type, PRMT5-overexpressing or doxorubicin-resistant MDA-MB-231 cells (5 × 106 per mouse, n = 5-7 for each group) were diluted in 100 uL of phosphate-buffered saline (PBS) plus 100 uL of Matrigel (BD Biosciences) and subcutaneously injected into female nude mice to investigate tumor growth. When all tumor volumes reached 100 mm3, the mice were randomly assigned and treated with the indicated drugs. In the experiment, doxorubicin was administered once a week via intravenous tail vein injection at 2 mg/kg body weight, and tadalafil was administered daily via oral gavage at 2 mg/kg body weight. Tumor volume was measured every 3 days using a digital caliper and calculated using the formula V = 1/2 × (diameter) × (smaller diameter)2. The mice were euthanized 27 days after injection.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	METTL3 promotes adriamycin resistance in MCF-7 breast cancer cells by accelerating pri-microRNA-221-3p maturation in a m6A-dependent manner. METTL3 knockdown was shown to reduce the expression of miR-221-3p by reducing pri-miR-221-3p m6A mRNA methylation, reducing the expression of MDR1 and Broad substrate specificity ATP-binding cassette transporter ABCG2 (BCRP/ABCG2), and inducing apoptosis. Identified the METTL3/miR-221-3p/HIPK2/Che-1 axis as a novel signaling event that will be responsible for resistance of BC cells to ADR.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell growth and death
	Cell apoptosis
In-vitro Model	ADR-resistant MCF-7 (MCF-7/ADR) cells (Human breast cancer doxorubicin-resistant cell line)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
In-vivo Model	Cell suspensions (2 × 106 cells/mL) made with MCF-7/ADR cells stably expressing METTL3 and/or miR-221-3p inhibitor were subcutaneously implanted into each mouse. One week later, xenografted mice were injected with 0.1 mL ADR (25 mg/kg, intraperitoneal injection) twice a week.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[10]
Response Summary	LNC942-METTL14-C-X-C chemokine receptor type 4 (CXCR4)/CYP1B1 signaling axis, which provides new targets and crosstalk m6A epigenetic modification mechanism for breast cancer prevention and treatment.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell apoptosis

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[11]
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]
Responsed Drug	Pertuzumab		Approved	Drug Info
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
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 by This Target Gene				[11]
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]
Responsed Drug	Trastuzumab		Approved	Drug Info
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
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 by This Target Gene				[11]
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]
Responsed Drug	Tucatinib		Approved	Drug Info
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
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.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	Knockdown of METTL3 downregulated protein levels of SOX2, CD133 and CD44 antigen (CD44) in MCF-7 cells. METTL3 is upregulated in breast cancer, and it promotes the stemness and malignant progression of BCa through mediating m6A modification on SOX2 mRNA.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[13]
Response Summary	METTL3 could down-regulate the expression of Collagen alpha-1 (III) chain (COL3A1) by increasing its m6A methylation, ultimately inhibiting the metastasis of TNBC cells.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[14]
Response Summary	The increased expression of Cyclic-AMP-dependent transcription factor ATF-3 (ATF3) in tamoxifen-resistant cells arises from the decreased expression of the m6A reader protein YTHDF2 and the ensuing elevated stability of ATF3 mRNA, which ultimately promotes the translation of ATF3. ATF3 as a candidate therapeutic target for mitigating drug resistance in breast cancer cells.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[15]
Response Summary	circMETTL3 promotes breast cancer progression through circMETTL3/miR-31-5p/Cyclin-dependent kinase 1 (CDK1) axis.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell cycle
In-vitro Model	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	HCC1806	Breast squamous cell carcinoma	Homo sapiens	CVCL_1258
	MCF-10A	Normal	Homo sapiens	CVCL_0598
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
In-vivo Model	Twelve female BALB/c nude mice (aged 4 weeks, 18-22g) were randomly divided into 2 groups. Stable circMETTL3-expression SUM1315 cells or control cells (1×106 cells in 0.1 mL PBS) was subcutaneously injected into mammary fat pads of the mice and the growth of tumors was followed up every week. Tumor volume was measured every week using a caliper, calculated as (length × width2)/2. After 4 weeks, mice were sacrificed and checked for final tumor weight.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[16]
Response Summary	KIAA1429 acts as an oncogenic factor in breast cancer by regulating CDK1 in an N6-methyladenosine-independent manner.5'-fluorouracil was found to be very effective in reducing the expression of KIAA1429 and Cyclin-dependent kinase 1 (CDK1) in breast cancer.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell proliferation and metastasis

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[17]
Response Summary	METTL3 is able to promote breast cancer cell proliferation by regulating the Cyclin-dependent kinase inhibitor 1 (CDKN1A) expression by an m6A-dependent manner. Metformin can take p21 as the main target to inhibit such effect.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	SUM1315MO2	Invasive breast carcinoma of no special type	Homo sapiens	CVCL_5589
	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
	HBL-100	Normal	Homo sapiens	CVCL_4362
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
In-vivo Model	About 1 × 107 stable METTL3 overexpression and negative control SUM-1315 cells were injected subcutaneously into the axilla of the female BALB/C nude mice (4-6 weeks old, 18-20 g, 10 mice/group). One week after injection, the two groups, METTL3 OE and NC, were then randomly allocated into the control group and experimental group (5 mice/group), which were treated with PBS or metformin (250 mg/kg/dose, respectively). PBS or metformin was administered every 2 days via intraperitoneal injection.

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[11]
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (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]
Responsed Drug	Pertuzumab		Approved	Drug Info
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
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 by This Target Gene				[11]
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (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]
Responsed Drug	Trastuzumab		Approved	Drug Info
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
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 by This Target Gene				[11]
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (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]
Responsed Drug	Tucatinib		Approved	Drug Info
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
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.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[10]
Response Summary	LNC942-METTL14-CXCR4/Cytochrome P450 1B1 (CYP1B1) signaling axis, which provides new targets and crosstalk m6A epigenetic modification mechanism for breast cancer prevention and treatment.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell apoptosis

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[18]
Response Summary	Knockdown of METTL3 sensitized these breast cancer cells to Adriamycin (ADR; also named as doxorubicin) treatment and increased accumulation of DNA damage. Mechanically, we demonstrated that inhibition of METTL3 impaired HR efficiency and increased ADR-induced DNA damage by regulating m6A modification of EGF/RAD51 axis. METTL3 promoted EGF expression through m6A modification, which further upregulated DNA repair protein RAD51 homolog 1 (RAD51) expression, resulting in enhanced HR activity.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Homologous recombination			hsa03440
Cell Process	Homologous recombination repair
In-vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
In-vivo Model	Cells were trypsinized and resuspended in DMEM at a consistence of 1 × 107 cells/ml. A total of 1 × 106 cells were injected into flank of mice. 27 days after injection, tumors were removed for paraffin-embedded sections.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[19]
Response Summary	KIAA1429 had the highest mutation frequency. Higher E3 ubiquitin-protein ligase Hakai (CBLL1) expression was associated with a better prognosis in breast cancer than lower CBLL1 expression.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell apoptosis

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[20]
Response Summary	Mechanistically, YTHDF3 enhances the translation of m6A-enriched transcripts for ST6GALNAC5, GJA1, and Epidermal growth factor receptor (EGFR), all associated with breast cancer brain metastasis. This work uncovers an essential role of YTHDF3 in controlling the interaction between cancer cells and brain microenvironment, thereby inducing brain metastatic competence.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	YTH domain-containing family protein 3 (YTHDF3)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell metastasis
In-vitro Model	MDA-MB-231Br (After brain metastases of MDA-MB-361 breast adenocarcinoma cells)
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MDA-IBC-3	Breast inflammatory carcinoma	Homo sapiens	CVCL_HC47
	JIMT-1Br3 (After brain metastases of JIMT-1 breast cancer cells)
	JIMT-1	Breast ductal carcinoma	Homo sapiens	CVCL_2077
	HEK293-FT	Normal	Homo sapiens	CVCL_6911
	HCC1954Br (After brain metastases of HCC1954 breast cancer cells)
	HCC1954	Breast ductal carcinoma	Homo sapiens	CVCL_1259
	bEnd.3	Cerebrovascular endothelioma cells from mice	Mus musculus	CVCL_0170
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	4T1Br (After brain metastases of 4T1 mouse breast cancer cells)
	4T1	Normal	Mus musculus	CVCL_0125
In-vivo Model	For the in vivo brain and bone extravasation and seeding assays, cancer cells labeled with CMFDA C2925 (Thermo fisher scientific) or GFP were injected intracardially into the nude mice. Cell number and injection procedure were described in "Animal Experiments". For the in vivo lung extravasation and seeding assays, cancer cells labeled with GFP (2.5 × 105 cells/mouse) were injected into the tail vein of nude mice. At 24 or 48 hrs later, the mice were sacrificed.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[21]
Response Summary	Epithelial membrane protein 3 (EMP3) blocks Akt-mTOR signaling activation and induces autophagy. EMP3 downregulates YTHDC1, which at least in part mediates the effects of EMP3 on breast cancer cells. EMP3 sensitizes breast cancer cells to the DNA-damaging drug Adriamycin. EMP3 downregulation can be responsible for breast cancer chemoresistance.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulator	YTH domain-containing protein 1 (YTHDC1)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Nucleotide excision repair			hsa03420
	mTOR signaling pathway			hsa04150
	PI3K-Akt signaling pathway			hsa04151
Cell Process	DNA repair
In-vitro Model	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	Hs 578T	Invasive breast carcinoma	Homo sapiens	CVCL_0332
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[11]
Response Summary	m6A-hypomethylation regulated Fibroblast growth factor receptor 4 (FGFR4) phosphorylates GSK-3beta and activates 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]
Responsed Drug	Pertuzumab		Approved	Drug Info
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
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 by This Target Gene				[11]
Response Summary	m6A-hypomethylation regulated Fibroblast growth factor receptor 4 (FGFR4) phosphorylates GSK-3beta and activates 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]
Responsed Drug	Trastuzumab		Approved	Drug Info
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
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 by This Target Gene				[11]
Response Summary	m6A-hypomethylation regulated Fibroblast growth factor receptor 4 (FGFR4) phosphorylates GSK-3beta and activates 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]
Responsed Drug	Tucatinib		Approved	Drug Info
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
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.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[22]
Response Summary	Forkhead box protein M1 (FOXM1) is a target of YTHDF1. Through recognizing and binding to the m6A-modified mRNA of FOXM1, YTHDF1 accelerated the translation process of FOXM1 and promoted breast cancer metastasis.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	Epithelial-mesenchymal transformation
	Cell proliferation
	Cell invasion
In-vitro Model	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	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
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
In-vivo Model	NOD/SCID immune-deficient mice were purchased from Shanghai Experimental Animal Center. 2 * 106 MCF-7 cells transduced with sh-NC or sh-YTHDF1-were subcutaneously injected into the mice (5/group). Tumor width and length were measured every 7 days. Tumor volume?=?(length * width2)/2. After 7 weeks, mice were sacrificed, and the weight of tumors was detected. Xenografts were collected for HE staining, immunohistochemistry staining and western blot analysis.For spontaneous lung metastasis assay, 4 * 106 sh-NC or sh-YTHDF1#2 transduced MCF-7 cells were injected into the mammary fat pads of the NOD/SCID mice (5/group). The primary tumor was removed when its volume reached 150 mm3. The mice were sacrificed, and lung metastasis nodules were counted 12 weeks after the removal.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[20]
Response Summary	Mechanistically, YTHDF3 enhances the translation of m6A-enriched transcripts for ST6GALNAC5, Gap junction alpha-1 protein (GJA1), and EGFR, all associated with breast cancer brain metastasis. This work uncovers an essential role of YTHDF3 in controlling the interaction between cancer cells and brain microenvironment, thereby inducing brain metastatic competence.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	YTH domain-containing family protein 3 (YTHDF3)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell metastasis
In-vitro Model	MDA-MB-231Br (After brain metastases of MDA-MB-361 breast adenocarcinoma cells)
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MDA-IBC-3	Breast inflammatory carcinoma	Homo sapiens	CVCL_HC47
	JIMT-1Br3 (After brain metastases of JIMT-1 breast cancer cells)
	JIMT-1	Breast ductal carcinoma	Homo sapiens	CVCL_2077
	HEK293-FT	Normal	Homo sapiens	CVCL_6911
	HCC1954Br (After brain metastases of HCC1954 breast cancer cells)
	HCC1954	Breast ductal carcinoma	Homo sapiens	CVCL_1259
	bEnd.3	Cerebrovascular endothelioma cells from mice	Mus musculus	CVCL_0170
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	4T1Br (After brain metastases of 4T1 mouse breast cancer cells)
	4T1	Normal	Mus musculus	CVCL_0125
In-vivo Model	For the in vivo brain and bone extravasation and seeding assays, cancer cells labeled with CMFDA C2925 (Thermo fisher scientific) or GFP were injected intracardially into the nude mice. Cell number and injection procedure were described in "Animal Experiments". For the in vivo lung extravasation and seeding assays, cancer cells labeled with GFP (2.5 × 105 cells/mouse) were injected into the tail vein of nude mice. At 24 or 48 hrs later, the mice were sacrificed.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[20]
Response Summary	Mechanistically, YTHDF3 enhances the translation of m6A-enriched transcripts for GD1 alpha synthase (ST6GALNAC5), GJA1, and EGFR, all associated with breast cancer brain metastasis. This work uncovers an essential role of YTHDF3 in controlling the interaction between cancer cells and brain microenvironment, thereby inducing brain metastatic competence.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	YTH domain-containing family protein 3 (YTHDF3)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell metastasis
In-vitro Model	MDA-MB-231Br (After brain metastases of MDA-MB-361 breast adenocarcinoma cells)
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MDA-IBC-3	Breast inflammatory carcinoma	Homo sapiens	CVCL_HC47
	JIMT-1Br3 (After brain metastases of JIMT-1 breast cancer cells)
	JIMT-1	Breast ductal carcinoma	Homo sapiens	CVCL_2077
	HEK293-FT	Normal	Homo sapiens	CVCL_6911
	HCC1954Br (After brain metastases of HCC1954 breast cancer cells)
	HCC1954	Breast ductal carcinoma	Homo sapiens	CVCL_1259
	bEnd.3	Cerebrovascular endothelioma cells from mice	Mus musculus	CVCL_0170
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	4T1Br (After brain metastases of 4T1 mouse breast cancer cells)
	4T1	Normal	Mus musculus	CVCL_0125
In-vivo Model	For the in vivo brain and bone extravasation and seeding assays, cancer cells labeled with CMFDA C2925 (Thermo fisher scientific) or GFP were injected intracardially into the nude mice. Cell number and injection procedure were described in "Animal Experiments". For the in vivo lung extravasation and seeding assays, cancer cells labeled with GFP (2.5 × 105 cells/mouse) were injected into the tail vein of nude mice. At 24 or 48 hrs later, the mice were sacrificed.

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[11]
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B) and activates 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]
Responsed Drug	Pertuzumab		Approved	Drug Info
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
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 by This Target Gene				[11]
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B) and activates 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]
Responsed Drug	Trastuzumab		Approved	Drug Info
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
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 by This Target Gene				[11]
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B) and activates 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]
Responsed Drug	Tucatinib		Approved	Drug Info
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
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.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[23]
Response Summary	Silencing METTL3 down-regulate MALAT1 and High mobility group protein HMGI-C (HMGA2) by sponging miR-26b, and finally inhibit EMT, migration and invasion in BC, providing a theoretical basis for clinical treatment of BC.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	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
In-vivo Model	Eighteen BALB/C female nude mice aged 4-5 weeks and weighing 15-18 g were randomly assigned into three groups of six mice. The MCF-7 cell lines stably transfected with sh-NC + oe-NC, sh-METTL3 + oe-NC and sh-METTL3 + oe-HMGA2 were selected for subcutaneous establishment of the BC cell line MCF-7 as xenografts in the nude mice. For this purpose, MCF-7 cell lines in the logarithmic growth stage were prepared into a suspension with a concentration of about 1 × 107 cells/ml. The prepared cell suspension was injected into the left armpit of the mice, and the subsequent tumor growth was recorded.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[24]
Response Summary	METTL3 is upregulated in Breast Cancer. It could regulate the protein level of Histone-lysine N-methyltransferase EZH2 (EZH2) through m6A modification to promote EMT and metastasis in BCa cells, thereafter aggravating the progression of BCa.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Adherens junction			hsa04520
In-vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[25]
Response Summary	Homeobox protein NANOG (NANOG) activity does not merely compensate for reduced O2 levels but significantly increases ALKBH5, JMJD2C, and TET1 activity in hypoxic breast cancer cells, leading to transcriptional and posttranscriptional changes in gene expression that promote the specification and/or maintenance of BCSCs. ALKBH5 overexpression decreased Homeobox protein NANOG (NANOG) mRNA methylation, increased NANOG levels, and increased the percentage of BCSCs,
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	HIF-1 signaling pathway			hsa04066
Cell Process	Signaling pathways regulating pluripotency of stem cells (hsa04550)
In-vitro Model	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	HCC1954	Breast ductal carcinoma	Homo sapiens	CVCL_1259
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MDA-MB-435	Amelanotic melanoma	Homo sapiens	CVCL_0417
	SUM-149 (Human breast cancer cell SUM149)
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	ZR75.1 A3	Invasive breast carcinoma	Homo sapiens	CVCL_YX82
In-vivo Model	A total of 1,000 breast cancer cells were injected into the mammary fat pad of 6-8-wk-old female NSG mice in a 1:1 suspension of Matrigel (BD Biosciences) in PBS solution. At 10 wk after injection, mice were examined for the presence of tumors, which were harvested for analysis.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[26]
Response Summary	ALKBH5 knockdown in MDA-MB-231 breast cancer cells significantly decreased metastasis from breast to lungs in immunodeficient mice. ALKBH5-mediated demethylation of N6-methyladenosine (m6A) in Homeobox protein NANOG (NANOG) mRNA leading to increased expression of NANOG.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
Cell Process	Biological regulation
	HIF-1 signaling pathway (hsa04066)
In-vitro Model	HCC1954	Breast ductal carcinoma	Homo sapiens	CVCL_1259
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	SUM-149 (Human breast cancer cell SUM149)
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	ZR75.1 A3	Invasive breast carcinoma	Homo sapiens	CVCL_YX82
In-vivo Model	1,000 MDA-MB-231 subclone cells were injected into the mammary fat pad of randomly chosen 6-to-8 week-old female severe combined immunodeficiency (SCID) mice in a 1:1 suspension of Matrigel (BD Biosciences) in PBS (n = 7 mice per subclone).
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[27]
Response Summary	In breast cancer, ZNF217 could upregulate Homeobox protein NANOG (NANOG) by reducing N6-methyladenosine levels via methyltransferase-like 13 (METTL3).
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell migration
	Cell invasion
	Epithelial-mesenchymal transition initiation

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	METTL3 promotes adriamycin resistance in MCF-7 breast cancer cells by accelerating pri-microRNA-221-3p maturation in a m6A-dependent manner. METTL3 knockdown was shown to reduce the expression of miR-221-3p by reducing pri-miR-221-3p m6A mRNA methylation, reducing the expression of MDR1 and BCRP, and inducing apoptosis. Identified the METTL3/miR-221-3p/Homeodomain-interacting protein kinase 2 (HIPK2)/Che-1 axis as a novel signaling event that will be responsible for resistance of BC cells to ADR.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell growth and death
	Cell apoptosis
In-vitro Model	ADR-resistant MCF-7 (MCF-7/ADR) cells (Human breast cancer doxorubicin-resistant cell line)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
In-vivo Model	Cell suspensions (2 × 106 cells/mL) made with MCF-7/ADR cells stably expressing METTL3 and/or miR-221-3p inhibitor were subcutaneously implanted into each mouse. One week later, xenografted mice were injected with 0.1 mL ADR (25 mg/kg, intraperitoneal injection) twice a week.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[28]
Response Summary	Specifically, increased METTL3 methylated KRT7-AS at A877 to increase the stability of a KRT7-AS/Keratin, type II cytoskeletal 7 (KRT7) mRNA duplex via IGF2BP1/HuR complexes. m6A promotes breast cancer lung metastasis by increasing the stability of a KRT7-AS/KRT7 mRNA duplex and translation of KRT7.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Lung Metastasis
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
In-vivo Model	First, subcutaneous transplanted model was used to evaluate the growth of BT-549LMF3 and BT-549 cells. Cells (5 × 106 per mouse, n = 5 for each group) were diluted in 200 ul PBS + 200 ul Matrigel (BD Biosciences) and subcutaneously injected into immunodeficient female mice. Second, subcutaneous transplanted model was used to evaluate the metastasis potential of BT-549LMF3 and BT-549 cells. Cells (5 × 106 per mouse, n = 5 for each group) were diluted in 200 ul PBS + 200 ul Matrigel (BD Biosciences) and subcutaneously injected into immunodeficient female mice. Third, the in vivo lung metastasis model was established by injecting with BT-549, BT-549LMF3, FTO stable BT-549LMF3, sh-METTL3 BT-549LMF3, and sh-KRT7 BT-549LMF3 stable cells (1 × 106 per mouse, n = 5 for each group)

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[29]
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 AKT and Mitogen-activated protein kinase 1 (MAPK/ERK2/MAPK1) that depend on A2B1 expression and are growth inhibited by inhibitors of these pathways.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Fulvestrant		Approved	Drug Info
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
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 by This Target Gene				[29]
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 AKT and Mitogen-activated protein kinase 1 (MAPK/ERK2/MAPK1) that depend on A2B1 expression and are growth inhibited by inhibitors of these pathways.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Tamoxifen		Approved	Drug Info
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
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

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[30]
Response Summary	LCAT3 upregulation is attributable to m6A modification mediated by METTL3, leading to LCAT3 stabilization. Treated cells with tamoxifen to induce MYC activity. Highlights the therapeutic potential of RBPs by uncovering a critical role for YTHDF2 in counteracting the global increase of mRNA synthesis in Myc proto-oncogene protein (MYC)-driven breast cancers.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Tamoxifen		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Pathway Response	MAPK signaling pathway			hsa04010
Cell Process	Epithelial-to-mesenchymal transition
	Cell apoptosis
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MBA-MD-231 (Human breast cancer cell)
	MYC-ER HMEC (Human mammary epithelial cells expressing a MYC estrogen receptor fusion)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
In-vivo Model	To induce recombination at 8 weeks of age both CAG-CreERT;Ythdf2fl/fl and Ythdf2fl/fl littermates were injected with 75mg/kg body weight tamoxifen dissolved in corn oil daily for 5 days.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[31]
Response Summary	Hypoxia-induced lncRNA KB-1980E6.3 is involved in the self-renewal and stemness maintenance of breast cancer stem cells by recruiting IGF2BP1 to regulate Myc proto-oncogene protein (MYC) mRNA stability.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Signaling pathways regulating pluripotency of stem cells			hsa04550
In-vitro Model	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	HEK293T	Normal	Homo sapiens	CVCL_0063
	Hs 578T	Invasive breast carcinoma	Homo sapiens	CVCL_0332
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
In-vivo Model	The enriched mammosphere cells derived from engineered BT549 and Hs578T with silenced lncRNA KB-1980E6.3 (shKB/vector), BT549, and Hs578T with lncRNA KB-1980E6.3 knockdown combined with ectopic c-Myc (shKB/c-Myc), BT549, and Hs578T with silenced IGF2BP1 (shIGF2BP1/vector), BT549, and Hs578T with knocked down IGF2BP1 combined with ectopic c-Myc (shIGF2BP1/c-Myc), and BT549, and Hs578T/shNC/vector control cells were used in Xenograft experiments. Three doses (1 × 105, 1 × 104 and 1 × 103) of spheres derived from the engineered Hs578T and 1 × 105 of spheres derived from the engineered BT549 were subcutaneously inoculated into 4- to 6-week-old female nude mice (n = 5 per group). Mice were then treated with either bevacizumab (10 mg/kg every 3 days) to form a hypoxic tumor microenvironment or vehicle PBS to form a non-hypoxic condition

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[18]
Response Summary	Knockdown of METTL3 sensitized these breast cancer cells to Adriamycin (ADR; also named as doxorubicin) treatment and increased accumulation of DNA damage. Mechanically, we demonstrated that inhibition of METTL3 impaired HR efficiency and increased ADR-induced DNA damage by regulating m6A modification of Pro-epidermal growth factor (EGF)/RAD51 axis. METTL3 promoted EGF expression through m6A modification, which further upregulated RAD51 expression, resulting in enhanced HR activity.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Homologous recombination			hsa03440
Cell Process	Homologous recombination repair
In-vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
In-vivo Model	Cells were trypsinized and resuspended in DMEM at a consistence of 1 × 107 cells/ml. A total of 1 × 106 cells were injected into flank of mice. 27 days after injection, tumors were removed for paraffin-embedded sections.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[32]
Response Summary	Programmed cell death 1 ligand 1 (CD274/PD-L1) was a downstream target of METTL3-mediated m6A modification in breast cancer cells. METTL3-mediated PD-L1 mRNA activation was m6A-IGF2BP3-dependent. PD-L1 expression was also positively correlated with METTL3 and IGF2BP3 expression in breast cancer tissues.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Tumor immune escape
In-vitro Model	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-10A	Normal	Homo sapiens	CVCL_0598
	HCC38	Breast ductal carcinoma	Homo sapiens	CVCL_1267
	4T1	Normal	Mus musculus	CVCL_0125
In-vivo Model	For subcutaneous xenograft experiments in B-NDG mice, approximately 1 × 106 MDA-MB-231 and there was subcutaneous injection of the cells that resuspended in 100 uL PBS into the left flank of the mice and were divided into 11 groups randomly (each containing 5 mice). After the treatment Atezolizumab (Selleck, Shanghai, China) or corresponding iso control antibody (Selleck, Shanghai, China) was injected intratumorally on day 3, 6, 9, 12, 15 post-MDA-MB-231 inoculations, and 5 × 106 cytokine-induced killer (CIK) cells were injected in the tail vein on day 7, 14, 21.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[32]
Response Summary	Programmed cell death 1 ligand 1 (CD274/PD-L1) was a downstream target of METTL3-mediated m6A modification in breast cancer cells. METTL3-mediated PD-L1 mRNA activation was m6A-IGF2BP3-dependent. PD-L1 expression was also positively correlated with METTL3 and IGF2BP3 expression in breast cancer tissues.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Tumor immune escape
In-vitro Model	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-10A	Normal	Homo sapiens	CVCL_0598
	HCC38	Breast ductal carcinoma	Homo sapiens	CVCL_1267
	4T1	Normal	Mus musculus	CVCL_0125
In-vivo Model	For subcutaneous xenograft experiments in B-NDG mice, approximately 1 × 106 MDA-MB-231 and there was subcutaneous injection of the cells that resuspended in 100 uL PBS into the left flank of the mice and were divided into 11 groups randomly (each containing 5 mice). After the treatment Atezolizumab (Selleck, Shanghai, China) or corresponding iso control antibody (Selleck, Shanghai, China) was injected intratumorally on day 3, 6, 9, 12, 15 post-MDA-MB-231 inoculations, and 5 × 106 cytokine-induced killer (CIK) cells were injected in the tail vein on day 7, 14, 21.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	Knockdown of METTL3 downregulated protein levels of SOX2, Prominin-1 (CD133) and CD44 in MCF-7 cells. METTL3 is upregulated in breast cancer, and it promotes the stemness and malignant progression of BCa through mediating m6A modification on SOX2 mRNA.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	METTL3 promotes adriamycin resistance in MCF-7 breast cancer cells by accelerating pri-microRNA-221-3p maturation in a m6A-dependent manner. METTL3 knockdown was shown to reduce the expression of miR-221-3p by reducing pri-miR-221-3p m6A mRNA methylation, reducing the expression of MDR1 and BCRP, and inducing apoptosis. Identified the METTL3/miR-221-3p/HIPK2/Protein AATF (AATF/CHE1) axis as a novel signaling event that will be responsible for resistance of BC cells to ADR.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell growth and death
	Cell apoptosis
In-vitro Model	ADR-resistant MCF-7 (MCF-7/ADR) cells (Human breast cancer doxorubicin-resistant cell line)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
In-vivo Model	Cell suspensions (2 × 106 cells/mL) made with MCF-7/ADR cells stably expressing METTL3 and/or miR-221-3p inhibitor were subcutaneously implanted into each mouse. One week later, xenografted mice were injected with 0.1 mL ADR (25 mg/kg, intraperitoneal injection) twice a week.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[33]
Response Summary	Tumor hypoxia can transcriptionally induce HIF1alpha and post-transcriptionally inhibit the expression of miR-16-5p to promote YTHDF1 expression, which could sequentially enhance tumor glycolysis by upregulating Pyruvate kinase PKM (PKM2/PKM) and eventually increase the tumorigenesis and metastasis potential of breast cancer cells.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	HIF-1 signaling pathway			hsa04066
Cell Process	Glycolysis
In-vitro Model	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	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
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
In-vivo Model	Each mouse was injected subcutaneously with 5 × 106 units of tumor cells to construct the tumor model.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[29]
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]
Responsed Drug	Fulvestrant		Approved	Drug Info
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
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 by This Target Gene				[29]
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]
Responsed Drug	Tamoxifen		Approved	Drug Info
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
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

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[34]
Response Summary	Ragulator complex protein LAMTOR5 (LAMTOR5/HBXIP) up-regulates METTL3 by suppressing let-7g, in which METTL3 increased HBXIP expression forming a positive feedback loop of HBXIP/let-7g/METTL3/HBXIP, leading to accelerated cell proliferation in breast cancer.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell differentiation and apoptosis
	Glutamine metabolism
	Apoptosis (hsa04210)

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[35]
Response Summary	HNRNPA2B1 is a reader of the N(6)-methyladenosine mark in primary-miRNAs and promotes Ribonuclease 3 (DROSHA) processing to precursor-miRNAs. HNRNPA2B1 downregulated miR-29a-3p, miR-29b-3p, and miR-222 and upregulated miR-1266-5p, miR-1268a, miR-671-3p. Transient overexpression of HNRNPA2/B1 reduced breast cancer cellMCF-7 sensitivity to 4-hydroxytamoxifen and fulvestrant, suggesting a role for HNRNPA2/B1 in endocrine-resistance.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Fulvestrant		Approved	Drug Info
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
Cell Process	Endocrine-resistance
In-vitro Model	MCF7/LCC9	Invasive breast carcinoma	Homo sapiens	CVCL_DP52
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[35]
Response Summary	HNRNPA2B1 is a reader of the N(6)-methyladenosine mark in primary-miRNAs and promotes Ribonuclease 3 (DROSHA) processing to precursor-miRNAs. HNRNPA2B1 downregulated miR-29a-3p, miR-29b-3p, and miR-222 and upregulated miR-1266-5p, miR-1268a, miR-671-3p. Transient overexpression of HNRNPA2/B1 reduced breast cancer cellMCF-7 sensitivity to 4-hydroxytamoxifen and fulvestrant, suggesting a role for HNRNPA2/B1 in endocrine-resistance.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Tamoxifen		Approved	Drug Info
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
Cell Process	Endocrine-resistance
In-vitro Model	MCF7/LCC9	Invasive breast carcinoma	Homo sapiens	CVCL_DP52
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[36]
Response Summary	Decreased doxorubicin resistance by Signal transducer and activator of transcription 3 (STAT3) knockdown was abolished by FTO overexpression and decreased doxorubicin sensitivity by STAT3 overexpression was reversed by FTO knockdown, indicating that FTO was implicated in STAT3-mediated doxorubicin resistance and impairment of doxorubicin sensitivity of BC cells.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	Hs 578T	Invasive breast carcinoma	Homo sapiens	CVCL_0332

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[37]
Response Summary	KIAA1429 could significantly promote the migration and invasion of breast cancer cells. KIAA1429 could bind to the motif in the 3' UTR of SMC protein 1A (SMC1A) mRNA directly and enhance SMC1A mRNA stability. In conclusion, the study revealed a novel mechanism of the KIAA1429/SMC1A/SNAIL axis in the regulation of metastasis of breast cancer.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Adherens junction			hsa04520
Cell Process	Epithelial-mesenchymal transition
	Cell migration
	Cell invasion
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	SUM1315MO2	Invasive breast carcinoma of no special type	Homo sapiens	CVCL_5589
In-vivo Model	For the mouse lung metastasis model, SUM-1315 cells (2 × 106/0.2 mL) expressing NC, shKIAA1429, SNAIL, or shKIAA1429+SNAIL were injected into the nude mice through the tail vein.

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[11]
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/Solute carrier family 40 member 1 (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]
Responsed Drug	Pertuzumab		Approved	Drug Info
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
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 by This Target Gene				[11]
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/Solute carrier family 40 member 1 (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]
Responsed Drug	Trastuzumab		Approved	Drug Info
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
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 by This Target Gene				[11]
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/Solute carrier family 40 member 1 (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]
Responsed Drug	Tucatinib		Approved	Drug Info
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
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.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	METTL3 can regulate the expression of MALAT1 through m6A, mediate the Transcription factor E2F1 (E2F1)/AGR2 axis, and promote the adriamycin resistance of breast cancer.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	MCF7-DoxR (Adriamycin-resistant cell line MCF7-DoxR)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
In-vivo Model	Once the tumor volume increased to about 1 cm3, six groups of MCF7 bearing mice (n = 10 in each group) were injected with PBS (0.1 ml, caudal vein) and adriamycin (0.1 ml, 10 mg/kg), respectively. When the tumor reached 1.5 cm in any direction (defined as event-free survival analysis), 10 mice in each group were selected to measure the tumor size and weight on the 12th day after adriamycin injection.

In total 6 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[38]
Response Summary	In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	RNA stability
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	Hs 578T	Invasive breast carcinoma	Homo sapiens	CVCL_0332
In-vivo Model	1×106 MDA-MB-231 cells were resuspended in 100 uL PBS with 50% Matrigel (Corning Costar, USA), and injected into the mammary fat pad of the mice.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[38]
Response Summary	In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	RNA stability
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	Hs 578T	Invasive breast carcinoma	Homo sapiens	CVCL_0332
In-vivo Model	1×106 MDA-MB-231 cells were resuspended in 100 uL PBS with 50% Matrigel (Corning Costar, USA), and injected into the mammary fat pad of the mice.
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[38]
Response Summary	In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	RNA stability
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	Hs 578T	Invasive breast carcinoma	Homo sapiens	CVCL_0332
In-vivo Model	1×106 MDA-MB-231 cells were resuspended in 100 uL PBS with 50% Matrigel (Corning Costar, USA), and injected into the mammary fat pad of the mice.
Experiment 4 Reporting the m6A-centered Disease Response by This Target Gene				[38]
Response Summary	In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	RNA stability
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	Hs 578T	Invasive breast carcinoma	Homo sapiens	CVCL_0332
In-vivo Model	1×106 MDA-MB-231 cells were resuspended in 100 uL PBS with 50% Matrigel (Corning Costar, USA), and injected into the mammary fat pad of the mice.
Experiment 5 Reporting the m6A-centered Disease Response by This Target Gene				[38]
Response Summary	In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Olaparib		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	RNA stability
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	Hs 578T	Invasive breast carcinoma	Homo sapiens	CVCL_0332
In-vivo Model	1×106 MDA-MB-231 cells were resuspended in 100 uL PBS with 50% Matrigel (Corning Costar, USA), and injected into the mammary fat pad of the mice.
Experiment 6 Reporting the m6A-centered Disease Response by This Target Gene				[38]
Response Summary	In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Olaparib		Approved	Drug Info
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	RNA stability
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	Hs 578T	Invasive breast carcinoma	Homo sapiens	CVCL_0332
In-vivo Model	1×106 MDA-MB-231 cells were resuspended in 100 uL PBS with 50% Matrigel (Corning Costar, USA), and injected into the mammary fat pad of the mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	Knockdown of METTL3 downregulated protein levels of Transcription factor SOX-2 (SOX2), CD133 and CD44 in MCF-7 cells. METTL3 is upregulated in breast cancer, and it promotes the stemness and malignant progression of BCa through mediating m6A modification on SOX2 mRNA.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[39]
Response Summary	YTHDF3 positively regulated cell migration, invasion, and EMT in triple-negative breast cancer cells. Moreover, Zinc finger E-box-binding homeobox 1 (ZEB1) was identified as a key downstream target for YTHDF3 and YTHDF3 could enhance ZEB1 mRNA stability in an m6A-dependent manner.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	YTH domain-containing family protein 3 (YTHDF3)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell migration
	Cell invasion
	Epithelial-mesenchymal transition
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	Hs 578T	Invasive breast carcinoma	Homo sapiens	CVCL_0332
	HCC1937	Breast ductal carcinoma	Homo sapiens	CVCL_0290
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[37]
Response Summary	KIAA1429 could significantly promote the migration and invasion of breast cancer cells. KIAA1429 could bind to the motif in the 3' UTR of SMC1A mRNA directly and enhance SMC1A mRNA stability. In conclusion, the study revealed a novel mechanism of the KIAA1429/SMC1A/Zinc finger protein SNAI1 (SNAI1) axis in the regulation of metastasis of breast cancer.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Adherens junction			hsa04520
Cell Process	Epithelial-mesenchymal transition
	Cell migration
	Cell invasion
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	SUM1315MO2	Invasive breast carcinoma of no special type	Homo sapiens	CVCL_5589
In-vivo Model	For the mouse lung metastasis model, SUM-1315 cells (2 × 106/0.2 mL) expressing NC, shKIAA1429, SNAIL, or shKIAA1429+SNAIL were injected into the nude mice through the tail vein.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[40]
Response Summary	LncRNA DLGAP1-AS1 promotes BC ADR-resistance through WTAP/DLGAP1 antisense RNA 1 (DLGAP1-AS1)/miR-299-3p feedback loop in breast cancer.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulator	Wilms tumor 1-associating protein (WTAP)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation
In-vitro Model	ADR-resistant MCF-7 (MCF-7/ADR) cells (Human breast cancer doxorubicin-resistant cell line)
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-10A	Normal	Homo sapiens	CVCL_0598

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[28]
Response Summary	Specifically, increased METTL3 methylated KRT7-AS at A877 to increase the stability of a KRT7-AS/KRT7 mRNA duplex via IGF2BP1/HuR complexes. m6A promotes breast cancer lung metastasis by increasing the stability of a KRT7-AS/KRT7 mRNA duplex and translation of KRT7.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Lung Metastasis
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
In-vivo Model	First, subcutaneous transplanted model was used to evaluate the growth of BT-549LMF3 and BT-549 cells. Cells (5 × 106 per mouse, n = 5 for each group) were diluted in 200 ul PBS + 200 ul Matrigel (BD Biosciences) and subcutaneously injected into immunodeficient female mice. Second, subcutaneous transplanted model was used to evaluate the metastasis potential of BT-549LMF3 and BT-549 cells. Cells (5 × 106 per mouse, n = 5 for each group) were diluted in 200 ul PBS + 200 ul Matrigel (BD Biosciences) and subcutaneously injected into immunodeficient female mice. Third, the in vivo lung metastasis model was established by injecting with BT-549, BT-549LMF3, FTO stable BT-549LMF3, sh-METTL3 BT-549LMF3, and sh-KRT7 BT-549LMF3 stable cells (1 × 106 per mouse, n = 5 for each group)

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[41]
Response Summary	m6A methyltransferase-like 3 (METTL3) gave rise to the upregulation of Long intergenic non-protein coding RNA 958 (LINC00958) by promoting its RNA transcript stability in breast cancer.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015
Cell Process	RNA transcript stability
In-vitro Model	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	MCF-10A	Normal	Homo sapiens	CVCL_0598
	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
In-vivo Model	MCF-7 cells transfected with sh-LINC00958 or empty vector were resuspended at 2 × 107 cells/mL.

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	METTL3 can regulate the expression of Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) through m6A, mediate the E2F1/AGR2 axis, and promote the adriamycin resistance of breast cancer.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	MCF7-DoxR (Adriamycin-resistant cell line MCF7-DoxR)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
In-vivo Model	Once the tumor volume increased to about 1 cm3, six groups of MCF7 bearing mice (n = 10 in each group) were injected with PBS (0.1 ml, caudal vein) and adriamycin (0.1 ml, 10 mg/kg), respectively. When the tumor reached 1.5 cm in any direction (defined as event-free survival analysis), 10 mice in each group were selected to measure the tumor size and weight on the 12th day after adriamycin injection.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[23]
Response Summary	Silencing METTL3 down-regulate Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and HMGA2 by sponging miR-26b, and finally inhibit EMT, migration and invasion in breast cancer, providing a theoretical basis for clinical treatment of breast cancer.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	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
	MCF-10A	Normal	Homo sapiens	CVCL_0598
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[23]
Response Summary	Silencing METTL3 down-regulate Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and HMGA2 by sponging miR-26b, and finally inhibit EMT, migration and invasion in BC, providing a theoretical basis for clinical treatment of BC.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	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
In-vivo Model	Eighteen BALB/C female nude mice aged 4-5 weeks and weighing 15-18 g were randomly assigned into three groups of six mice. The MCF-7 cell lines stably transfected with sh-NC + oe-NC, sh-METTL3 + oe-NC and sh-METTL3 + oe-HMGA2 were selected for subcutaneous establishment of the BC cell line MCF-7 as xenografts in the nude mice. For this purpose, MCF-7 cell lines in the logarithmic growth stage were prepared into a suspension with a concentration of about 1 × 107 cells/ml. The prepared cell suspension was injected into the left armpit of the mice, and the subsequent tumor growth was recorded.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[35]
Response Summary	HNRNPA2B1 is a reader of the N(6)-methyladenosine mark in primary-miRNAs and promotes DROSHA processing to precursor-miRNAs. HNRNPA2B1 downregulated miR-29a-3p, miR-29b-3p, and microRNA 222 (MIR222) and upregulated miR-1266-5p, miR-1268a, miR-671-3p. Transient overexpression of HNRNPA2/B1 reduced breast cancer cellMCF-7 sensitivity to 4-hydroxytamoxifen and fulvestrant, suggesting a role for HNRNPA2/B1 in endocrine-resistance.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Fulvestrant		Approved	Drug Info
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
Cell Process	Endocrine-resistance
In-vitro Model	MCF7/LCC9	Invasive breast carcinoma	Homo sapiens	CVCL_DP52
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[35]
Response Summary	HNRNPA2B1 is a reader of the N(6)-methyladenosine mark in primary-miRNAs and promotes DROSHA processing to precursor-miRNAs. HNRNPA2B1 downregulated miR-29a-3p, miR-29b-3p, and microRNA 222 (MIR222) and upregulated miR-1266-5p, miR-1268a, miR-671-3p. Transient overexpression of HNRNPA2/B1 reduced breast cancer cellMCF-7 sensitivity to 4-hydroxytamoxifen and fulvestrant, suggesting a role for HNRNPA2/B1 in endocrine-resistance.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Tamoxifen		Approved	Drug Info
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
Cell Process	Endocrine-resistance
In-vitro Model	MCF7/LCC9	Invasive breast carcinoma	Homo sapiens	CVCL_DP52
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[34]
Response Summary	HBXIP up-regulates METTL3 by suppressing microRNA let-7g (MIRLET7G), in which METTL3 increased HBXIP expression forming a positive feedback loop of HBXIP/let-7g/METTL3/HBXIP, leading to accelerated cell proliferation in breast cancer.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Cell Process	Cell differentiation and apoptosis
	Glutamine metabolism
	Apoptosis (hsa04210)

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[35]
Response Summary	HNRNPA2B1 is a reader of the N(6)-methyladenosine mark in primary-miRNAs and promotes DROSHA processing to precursor-miRNAs. HNRNPA2B1 downregulated miR-29a-3p, miR-29b-3p, and miR-222 and upregulated hsa-miR-1266-5p, miR-1268a, miR-671-3p. Transient overexpression of HNRNPA2/B1 reduced breast cancer cellMCF-7 sensitivity to 4-hydroxytamoxifen and fulvestrant, suggesting a role for HNRNPA2/B1 in endocrine-resistance.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Fulvestrant		Approved	Drug Info
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
Cell Process	Endocrine-resistance
In-vitro Model	MCF7/LCC9	Invasive breast carcinoma	Homo sapiens	CVCL_DP52
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[35]
Response Summary	HNRNPA2B1 is a reader of the N(6)-methyladenosine mark in primary-miRNAs and promotes DROSHA processing to precursor-miRNAs. HNRNPA2B1 downregulated miR-29a-3p, miR-29b-3p, and miR-222 and upregulated hsa-miR-1266-5p, miR-1268a, miR-671-3p. Transient overexpression of HNRNPA2/B1 reduced breast cancer cellMCF-7 sensitivity to 4-hydroxytamoxifen and fulvestrant, suggesting a role for HNRNPA2/B1 in endocrine-resistance.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Tamoxifen		Approved	Drug Info
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
Cell Process	Endocrine-resistance
In-vitro Model	MCF7/LCC9	Invasive breast carcinoma	Homo sapiens	CVCL_DP52
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[35]
Response Summary	HNRNPA2B1 is a reader of the N(6)-methyladenosine mark in primary-miRNAs and promotes DROSHA processing to precursor-miRNAs. HNRNPA2B1 downregulated miR-29a-3p, miR-29b-3p, and miR-222 and upregulated miR-1266-5p, hsa-miR-1268a, miR-671-3p. Transient overexpression of HNRNPA2/B1 reduced breast cancer cellMCF-7 sensitivity to 4-hydroxytamoxifen and fulvestrant, suggesting a role for HNRNPA2/B1 in endocrine-resistance.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Fulvestrant		Approved	Drug Info
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
Cell Process	Endocrine-resistance
In-vitro Model	MCF7/LCC9	Invasive breast carcinoma	Homo sapiens	CVCL_DP52
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[35]
Response Summary	HNRNPA2B1 is a reader of the N(6)-methyladenosine mark in primary-miRNAs and promotes DROSHA processing to precursor-miRNAs. HNRNPA2B1 downregulated miR-29a-3p, miR-29b-3p, and miR-222 and upregulated miR-1266-5p, hsa-miR-1268a, miR-671-3p. Transient overexpression of HNRNPA2/B1 reduced breast cancer cellMCF-7 sensitivity to 4-hydroxytamoxifen and fulvestrant, suggesting a role for HNRNPA2/B1 in endocrine-resistance.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Tamoxifen		Approved	Drug Info
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
Cell Process	Endocrine-resistance
In-vitro Model	MCF7/LCC9	Invasive breast carcinoma	Homo sapiens	CVCL_DP52
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[42]
Response Summary	In breast cancer, hsa-miR-146a-5p modulated by METTL14 promoted cell migration and invasion.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell migration and invasion
	Epithelial-mesenchymal transition
In-vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	FTO up-regulated ARL5B by inhibiting hsa-miR-181b-3p. The carcinogenic activity of FTO in promoting the invasion and migration of breast cancer cells via the FTO/miR-181b-3p/ARL5B signaling pathway.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Down regulation
Cell Process	Cell invasion and migration
In-vitro Model	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	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
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	METTL3 promotes adriamycin resistance in MCF-7 breast cancer cells by accelerating hsa-miR-221-3p maturation in a m6A-dependent manner. METTL3 knockdown was shown to reduce the expression of miR-221-3p by reducing pri-miR-221-3p m6A mRNA methylation, reducing the expression of MDR1 and BCRP, and inducing apoptosis. Identified the METTL3/miR-221-3p/HIPK2/Che-1 axis as a novel signaling event that will be responsible for resistance of BC cells to ADR.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell growth and death
	Cell apoptosis
In-vitro Model	ADR-resistant MCF-7 (MCF-7/ADR) cells (Human breast cancer doxorubicin-resistant cell line)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
In-vivo Model	Cell suspensions (2 × 106 cells/mL) made with MCF-7/ADR cells stably expressing METTL3 and/or miR-221-3p inhibitor were subcutaneously implanted into each mouse. One week later, xenografted mice were injected with 0.1 mL ADR (25 mg/kg, intraperitoneal injection) twice a week.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[23]
Response Summary	Silencing METTL3 down-regulate MALAT1 and HMGA2 by sponging hsa-miR-26b, and finally inhibit EMT, migration and invasion in BC, providing a theoretical basis for clinical treatment of BC.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	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
In-vivo Model	Eighteen BALB/C female nude mice aged 4-5 weeks and weighing 15-18 g were randomly assigned into three groups of six mice. The MCF-7 cell lines stably transfected with sh-NC + oe-NC, sh-METTL3 + oe-NC and sh-METTL3 + oe-HMGA2 were selected for subcutaneous establishment of the BC cell line MCF-7 as xenografts in the nude mice. For this purpose, MCF-7 cell lines in the logarithmic growth stage were prepared into a suspension with a concentration of about 1 × 107 cells/ml. The prepared cell suspension was injected into the left armpit of the mice, and the subsequent tumor growth was recorded.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[35]
Response Summary	HNRNPA2B1 is a reader of the N(6)-methyladenosine mark in primary-miRNAs and promotes DROSHA processing to precursor-miRNAs. HNRNPA2B1 downregulated hsa-miR-29a-3p, miR-29b-3p, and miR-222 and upregulated miR-1266-5p, miR-1268a, miR-671-3p. Transient overexpression of HNRNPA2/B1 reduced breast cancer cellMCF-7 sensitivity to 4-hydroxytamoxifen and fulvestrant, suggesting a role for HNRNPA2/B1 in endocrine-resistance.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Fulvestrant		Approved	Drug Info
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
Cell Process	Endocrine-resistance
In-vitro Model	MCF7/LCC9	Invasive breast carcinoma	Homo sapiens	CVCL_DP52
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[35]
Response Summary	HNRNPA2B1 is a reader of the N(6)-methyladenosine mark in primary-miRNAs and promotes DROSHA processing to precursor-miRNAs. HNRNPA2B1 downregulated hsa-miR-29a-3p, miR-29b-3p, and miR-222 and upregulated miR-1266-5p, miR-1268a, miR-671-3p. Transient overexpression of HNRNPA2/B1 reduced breast cancer cellMCF-7 sensitivity to 4-hydroxytamoxifen and fulvestrant, suggesting a role for HNRNPA2/B1 in endocrine-resistance.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Tamoxifen		Approved	Drug Info
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
Cell Process	Endocrine-resistance
In-vitro Model	MCF7/LCC9	Invasive breast carcinoma	Homo sapiens	CVCL_DP52
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[35]
Response Summary	HNRNPA2B1 is a reader of the N(6)-methyladenosine mark in primary-miRNAs and promotes DROSHA processing to precursor-miRNAs. HNRNPA2B1 downregulated miR-29a-3p, hsa-miR-29b-3p, and miR-222 and upregulated miR-1266-5p, miR-1268a, miR-671-3p. Transient overexpression of HNRNPA2/B1 reduced breast cancer cellMCF-7 sensitivity to 4-hydroxytamoxifen and fulvestrant, suggesting a role for HNRNPA2/B1 in endocrine-resistance.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Fulvestrant		Approved	Drug Info
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
Cell Process	Endocrine-resistance
In-vitro Model	MCF7/LCC9	Invasive breast carcinoma	Homo sapiens	CVCL_DP52
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[35]
Response Summary	HNRNPA2B1 is a reader of the N(6)-methyladenosine mark in primary-miRNAs and promotes DROSHA processing to precursor-miRNAs. HNRNPA2B1 downregulated miR-29a-3p, hsa-miR-29b-3p, and miR-222 and upregulated miR-1266-5p, miR-1268a, miR-671-3p. Transient overexpression of HNRNPA2/B1 reduced breast cancer cellMCF-7 sensitivity to 4-hydroxytamoxifen and fulvestrant, suggesting a role for HNRNPA2/B1 in endocrine-resistance.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Tamoxifen		Approved	Drug Info
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
Cell Process	Endocrine-resistance
In-vitro Model	MCF7/LCC9	Invasive breast carcinoma	Homo sapiens	CVCL_DP52
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[15]
Response Summary	circMETTL3 promotes breast cancer progression through circMETTL3/hsa-miR-31-5p/CDK1 axis.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell cycle
In-vitro Model	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	HCC1806	Breast squamous cell carcinoma	Homo sapiens	CVCL_1258
	MCF-10A	Normal	Homo sapiens	CVCL_0598
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
In-vivo Model	Twelve female BALB/c nude mice (aged 4 weeks, 18-22g) were randomly divided into 2 groups. Stable circMETTL3-expression SUM1315 cells or control cells (1×106 cells in 0.1 mL PBS) was subcutaneously injected into mammary fat pads of the mice and the growth of tumors was followed up every week. Tumor volume was measured every week using a caliper, calculated as (length × width2)/2. After 4 weeks, mice were sacrificed and checked for final tumor weight.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[35]
Response Summary	HNRNPA2B1 is a reader of the N(6)-methyladenosine mark in primary-miRNAs and promotes DROSHA processing to precursor-miRNAs. HNRNPA2B1 downregulated miR-29a-3p, miR-29b-3p, and miR-222 and upregulated miR-1266-5p, miR-1268a, hsa-miR-671-3p. Transient overexpression of HNRNPA2/B1 reduced breast cancer cellMCF-7 sensitivity to 4-hydroxytamoxifen and fulvestrant, suggesting a role for HNRNPA2/B1 in endocrine-resistance.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Fulvestrant		Approved	Drug Info
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
Cell Process	Endocrine-resistance
In-vitro Model	MCF7/LCC9	Invasive breast carcinoma	Homo sapiens	CVCL_DP52
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[35]
Response Summary	HNRNPA2B1 is a reader of the N(6)-methyladenosine mark in primary-miRNAs and promotes DROSHA processing to precursor-miRNAs. HNRNPA2B1 downregulated miR-29a-3p, miR-29b-3p, and miR-222 and upregulated miR-1266-5p, miR-1268a, hsa-miR-671-3p. Transient overexpression of HNRNPA2/B1 reduced breast cancer cellMCF-7 sensitivity to 4-hydroxytamoxifen and fulvestrant, suggesting a role for HNRNPA2/B1 in endocrine-resistance.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Tamoxifen		Approved	Drug Info
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
Cell Process	Endocrine-resistance
In-vitro Model	MCF7/LCC9	Invasive breast carcinoma	Homo sapiens	CVCL_DP52
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[31]
Response Summary	Hypoxia-induced lncRNA KB-1980E6.3 is involved in the self-renewal and stemness maintenance of breast cancer stem cells by recruiting IGF2BP1 to regulate c-Myc mRNA stability.
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Signaling pathways regulating pluripotency of stem cells			hsa04550
In-vitro Model	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	HEK293T	Normal	Homo sapiens	CVCL_0063
	Hs 578T	Invasive breast carcinoma	Homo sapiens	CVCL_0332
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
In-vivo Model	The enriched mammosphere cells derived from engineered BT549 and Hs578T with silenced lncRNA KB-1980E6.3 (shKB/vector), BT549, and Hs578T with lncRNA KB-1980E6.3 knockdown combined with ectopic c-Myc (shKB/c-Myc), BT549, and Hs578T with silenced IGF2BP1 (shIGF2BP1/vector), BT549, and Hs578T with knocked down IGF2BP1 combined with ectopic c-Myc (shIGF2BP1/c-Myc), and BT549, and Hs578T/shNC/vector control cells were used in Xenograft experiments. Three doses (1 × 105, 1 × 104 and 1 × 103) of spheres derived from the engineered Hs578T and 1 × 105 of spheres derived from the engineered BT549 were subcutaneously inoculated into 4- to 6-week-old female nude mice (n = 5 per group). Mice were then treated with either bevacizumab (10 mg/kg every 3 days) to form a hypoxic tumor microenvironment or vehicle PBS to form a non-hypoxic condition