m6A-centered Drug Response Information

General Information of the Drug (ID: M6ADRUG0022)
Name
Doxil
Synonyms
doxorubicin; 23214-92-8; Doxil; Doxorubicine; Adriablastin; Doxorubicinum; 14-Hydroxydaunomycin; 14-Hydroxydaunorubicine; Doxorubicina; Adriamycin semiquinone; Doxorubicinum [INN-Latin]; Doxorubicine [INN-French]; Doxorubicina [INN-Spanish]; Myocet; FI 106; Doxorubicin [USAN:INN:BAN]; CCRIS 739; NDC 38242-874; HSDB 3070; UNII-80168379AG; NCI-C01514; EINECS 245-495-6; CHEMBL53463; CHEBI:28748; 5,12-Naphthacenedione,; ADM; ADR; ThermoDox; Aerosolized Doxorubicin; Doxorubicin citrate; RDF Rubex; Conjugate of doxorubicin with humanized monoclonal antibody LL1 against CD74; DM2; JT9100000; Adiblastine (hydrochloride salt); Adr iablatina (hydrochloride salt); Adriablastine (hydrochloride salt); Adriablatina (hydrochloride salt); Adriacin (hydrochloride salt); Adriamycin PFS (TN); Adriamycin PFS (hydrochloride salt); Adriamycin RDF (TN); Adriamycin RDF (hydrochloride salt); Adriblastina (TN); Adriblastina (hydrochloride salt); Adriblatina (hydrochloride salt); Caelyx (TN); Conjugate of doxorubicin with monoclonal antibody P4/D10 against GP120; DOX-SL; Doxorubicin hydrochloride (hydrochloride salt); Doxorubicin-hLL1; Doxorubicin-hLL1 conjugate; Farmablastina (hydrochloride salt); Hydroxydaunomycin hydrochlor ide (hydrochloride salt); Hydroxydaunomycin hydrochloride (hydrochloride salt); Hydroxydaunorubicin hydrochloride (hydrochloride salt); Myocet (TN); Rubex (TN); Rubex (hydrochloride salt); TLC D-99; Doxorubicin (USAN/INN); Doxorubicin-P4/D10; Doxorubicin-P4/D10 conjugate; Cantide + adriamycin
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Status Approved [1]
Structure
Formula
C27H29NO11
InChI
InChI=1S/C27H29NO11/c1-10-22(31)13(28)6-17(38-10)39-15-8-27(36,16(30)9-29)7-12-19(15)26(35)21-20(24(12)33)23(32)11-4-3-5-14(37-2)18(11)25(21)34/h3-5,10,13,15,17,22,29,31,33,35-36H,6-9,28H2,1-2H3/t10-,13-,15-,17-,22+,27-/m0/s1
InChIKey
AOJJSUZBOXZQNB-TZSSRYMLSA-N
PubChem CID
31703
TTD Drug ID
D07VLY
DrugBank ID
DB00997
Full List of m6A Targets Related to This Drug
Anterior gradient protein 2 homolog (AGR2)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [2]
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
 Disease 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.
ATP-dependent translocase ABCB1 (ABCB1)
 Target Info 
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [3]
Response Summary IGF2BP3, directly bound to the m6A-modified region of ATP-dependent translocase ABCB1 (ABCB1) mRNA, thereby promoting the stability and expression of ABCB1 mRNA. The expression of IGF2BP3 and ABCB1 was strongly correlated with DOX sensitivity. Targeting IGF2BP3 was an important chemotherapeutic strategy for preventing MDR development in colorectal cancer.
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response ABC transporters hsa02010
Cell Process RNA stability
In-vitro Model DLD-1 Colon adenocarcinoma Homo sapiens CVCL_0248
HCT 116 Colon carcinoma Homo sapiens CVCL_0291
HCT 15 Colon adenocarcinoma Homo sapiens CVCL_0292
HCT 8 Colon adenocarcinoma Homo sapiens CVCL_2478
HT29 Colon cancer Mus musculus CVCL_A8EZ
SW1463 Rectal adenocarcinoma Homo sapiens CVCL_1718
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
SW620 Colon adenocarcinoma Homo sapiens CVCL_0547
In-vivo Model HCT8/T xenografts derived from shNC or shIGF2BP3-1 HCT8/T cells were established through subcutaneous inoculation of cells (6×106) into nude mice.
Experiment 2 Reporting the m6A-centered Drug Response by This Target Gene [4]
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
 Disease 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.
Breast cancer type 1 susceptibility protein (BRCA1)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [5]
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
 Disease 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.
Broad substrate specificity ATP-binding cassette transporter ABCG2 (BCRP/ABCG2)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [4]
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
 Disease 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.
DNA repair protein RAD51 homolog 1 (RAD51)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [6]
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
 Disease 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.
Epithelial membrane protein 3 (EMP3)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [7]
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
 Disease 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
Homeodomain-interacting protein kinase 2 (HIPK2)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [4]
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
 Disease 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.
NAD-dependent protein deacetylase sirtuin-1 (SIRT1)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [8]
Response Summary The elevated m6A RNA levels and the most upregulated METTL14 expression in kidneys of mice with adriamycin and diabetic nephropathy. METTL14-dependent RNA m6A modification contributes to podocyte injury through posttranscriptional regulation of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) mRNA, which provide a potential approach for the diagnosis and treatment of podocytopathies.
Responsed Disease Chronic kidney disease ICD-11: GB61.Z
 Disease Info 
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Cell Process Cell apoptosis
In-vitro Model Conditionally immortalized human podocytes (Podocytes)
In-vivo Model To establish mice model with ADR nephropathy, adult male C57BL/6J mice (8-12 weeks of age) were purchased from Animal Center of Fudan University and injected with 19.5 mg/kg ADR (D1515, Sigma-Aldrich, St-Louis, MO, USA) intravenously via tail vein.
Pro-epidermal growth factor (EGF)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [6]
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
 Disease 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.
Protein AATF (AATF/CHE1)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [4]
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
 Disease 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.
Signal transducer and activator of transcription 3 (STAT3)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [9]
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
 Disease 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
Transcription factor E2F1 (E2F1)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [2]
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
 Disease 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.
Transcription factor E2F8 (E2F8)
 Target Info 
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [10]
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
 Disease 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 Drug Response by This Target Gene [10]
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
 Disease 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.
DLGAP1 antisense RNA 1 (DLGAP1-AS1)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [11]
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
 Disease 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
Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [2]
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
 Disease 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.
hsa-miR-221-3p
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [4]
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
 Disease 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.
References
Ref 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7069).
Ref 2 Effect of m6A methyltransferase METTL3 -mediated MALAT1/E2F1/AGR2 axis on adriamycin resistance in breast cancer. J Biochem Mol Toxicol. 2022 Jan;36(1):e22922. doi: 10.1002/jbt.22922. Epub 2021 Dec 28.
Ref 3 Binding of RNA m6A by IGF2BP3 triggers chemoresistance of HCT8 cells via upregulation of ABCB1. Am J Cancer Res. 2021 Apr 15;11(4):1428-1445. eCollection 2021.
Ref 4 METTL3 promotes adriamycin resistance in MCF-7 breast cancer cells by accelerating pri-microRNA-221-3p maturation in a m6A-dependent manner. Exp Mol Med. 2021 Jan;53(1):91-102. doi: 10.1038/s12276-020-00510-w. Epub 2021 Jan 8.
Ref 5 PRMT5 regulates RNA m6A demethylation for doxorubicin sensitivity in breast cancer. Mol Ther. 2022 Jul 6;30(7):2603-2617. doi: 10.1016/j.ymthe.2022.03.003. Epub 2022 Mar 10.
Ref 6 METTL3 promotes homologous recombination repair and modulates chemotherapeutic response in breast cancer by regulating the EGF/RAD51 axis. Elife. 2022 May 3;11:e75231. doi: 10.7554/eLife.75231.
Ref 7 EMP3 negatively modulates breast cancer cell DNA replication, DNA damage repair, and stem-like properties. Cell Death Dis. 2021 Sep 12;12(9):844. doi: 10.1038/s41419-021-04140-6.
Ref 8 METTL14 aggravates podocyte injury and glomerulopathy progression through N(6)-methyladenosine-dependent downregulating of Sirt1. Cell Death Dis. 2021 Sep 27;12(10):881. doi: 10.1038/s41419-021-04156-y.
Ref 9 Fat mass and obesity-associated protein (FTO) mediates signal transducer and activator of transcription 3 (STAT3)-drived resistance of breast cancer to doxorubicin. Bioengineered. 2021 Dec;12(1):1874-1889. doi: 10.1080/21655979.2021.1924544.
Ref 10 YTHDF1 promotes breast cancer cell growth, DNA damage repair and chemoresistance. Cell Death Dis. 2022 Mar 12;13(3):230. doi: 10.1038/s41419-022-04672-5.
Ref 11 N(6)-methyladenosine (m(6)A)-mediated lncRNA DLGAP1-AS1enhances breast canceradriamycin resistance through miR-299-3p/WTAP feedback loop. Bioengineered. 2021 Dec;12(2):10935-10944. doi: 10.1080/21655979.2021.2000198.