m6A-centered Drug Response Information
General Information of the Drug (ID: M6ADRUG0048)
| Name |
Oxaliplatin
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| Synonyms |
Eloxatin (TN); Medac (TN); Oxaliplatin (TN); Oxaliplatin (JAN/USAN/INN)
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| Status | Approved | [1] | |||
| Structure |
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3D MOL
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| Formula |
C8H14N2O4Pt
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| InChI |
InChI=1S/C6H12N2.C2H2O4.Pt/c7-5-3-1-2-4-6(5)8;3-1(4)2(5)6;/h5-8H,1-4H2;(H,3,4)(H,5,6);/q-2;;+2/t5-,6-;;/m1../s1
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| InChIKey |
DRMCATBEKSVAPL-BNTLRKBRSA-N
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Full List of m6A Targets Related to This Drug
Poly [ADP-ribose] polymerase 1 (PARP1)
| In total 2 item(s) under this target gene | ||||
| Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene | [4] | |||
| Response Summary | m6A methyltransferase METTL3 facilitates oxaliplatin resistance in CD133+ gastric cancer stem cells by Promoting Poly [ADP-ribose] polymerase 1 (PARP1) mRNA stability which increases base excision repair pathway activity. METTTL3 enhances the stability of PARP1 by recruiting YTHDF1 to target the 3'-untranslated Region (3'-UTR) of PARP1 mRNA. | |||
| Responsed Disease | Gastric cancer | ICD-11: 2B72 | ||
| Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
| Target Regulation | Up regulation | |||
| Pathway Response | Nucleotide excision repair | hsa03420 | ||
| Signaling pathways regulating pluripotency of stem cells | hsa04550 | |||
| Cell Process | RNA stability | |||
| Excision repair | ||||
| In-vitro Model | SNU-719 | Gastric tubular adenocarcinoma | Homo sapiens | CVCL_5086 |
| MKN74 | Gastric tubular adenocarcinoma | Homo sapiens | CVCL_2791 | |
| HEK293T | Normal | Homo sapiens | CVCL_0063 | |
| AGS | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | |
| In-vivo Model | 100,000 pLKO and PARP1-sh1 (PT1 and PT2) cells were mixed with matrix gel and inoculate into BALB/C nude mice, respectively. After 25 days, 6 organoid transplanted tumor mice were treated with oxaliplatin (Sellekchem, s1224) twice a week for 4 weeks at a dose of 5 mg/kg. | |||
| Experiment 2 Reporting the m6A-centered Drug Response by This Target Gene | [4] | |||
| Response Summary | m6A methyltransferase METTL3 facilitates oxaliplatin resistance in CD133+ gastric cancer stem cells by Promoting PARP1 mRNA stability which increases base excision repair pathway activity. METTTL3 enhances the stability of PARP1 by recruiting Poly [ADP-ribose] polymerase 1 (PARP1) to target the 3'-untranslated Region (3'-UTR) of PARP1 mRNA. | |||
| Responsed Disease | Gastric cancer | ICD-11: 2B72 | ||
| Target Regulator | YTH domain-containing family protein 1 (YTHDF1) | READER | ||
| Target Regulation | Up regulation | |||
| Pathway Response | Nucleotide excision repair | hsa03420 | ||
| Signaling pathways regulating pluripotency of stem cells | hsa04550 | |||
| Cell Process | RNA stability | |||
| Excision repair | ||||
| In-vitro Model | SNU-719 | Gastric tubular adenocarcinoma | Homo sapiens | CVCL_5086 |
| MKN74 | Gastric tubular adenocarcinoma | Homo sapiens | CVCL_2791 | |
| HEK293T | Normal | Homo sapiens | CVCL_0063 | |
| AGS | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | |
| In-vivo Model | 100,000 pLKO and PARP1-sh1 (PT1 and PT2) cells were mixed with matrix gel and inoculate into BALB/C nude mice, respectively. After 25 days, 6 organoid transplanted tumor mice were treated with oxaliplatin (Sellekchem, s1224) twice a week for 4 weeks at a dose of 5 mg/kg. | |||
TNF receptor-associated factor 5 (TRAF5)
| In total 1 item(s) under this target gene | ||||
| Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene | [5] | |||
| Response Summary | 2-polarized tumor-associated macrophages enabled the oxaliplatin resistance via the elevation of METTL3-mediated m6A modification in Colorectal Cancer cells. Furthermore, they found that TNF receptor-associated factor 5 (TRAF5) contributes to the METTL3-triggered OX resistance in CRC cells. | |||
| Responsed Disease | Colorectal cancer | ICD-11: 2B91 | ||
| Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
| Target Regulation | Down regulation | |||
| In-vitro Model | LoVo | Colon adenocarcinoma | Homo sapiens | CVCL_0399 |
| HCT 116 | Colon carcinoma | Homo sapiens | CVCL_0291 | |
| In-vivo Model | HCT-116 cells (3 × 105 cells in 200 uL of saline) were subcutaneously injected into the nude mice to establish xenograft tumors. After 10 days, 10 mg/kg OX or saline was intraperitoneally injected (n = 5 for each group). Si-METTL3 or si-TRAF5 (10 nmol/20 g body weight) was injected twice intratumorally before the start of OX treatment. The mice were examined every 2 days and sacrificed 4 weeks after the OX treatment. | |||
Translocation protein SEC62 (SEC62)
| In total 1 item(s) under this target gene | ||||
| Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene | [6] | |||
| Response Summary | Translocation protein SEC62 (SEC62) upregulated by the METTL3-mediated m6A modification promotes the stemness and chemoresistance of colorectal cancer by binding to beta-catenin and enhancing Wnt signalling. Depletion of Sec62 sensitized the CRC cells to 5-Fu or oxaliplatin treatment. | |||
| Responsed Disease | Colorectal cancer | ICD-11: 2B91 | ||
| Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
| Target Regulation | Up regulation | |||
| Pathway Response | Wnt signaling pathway | hsa04310 | ||
| Cell Process | Protein degradation | |||
| In-vitro Model | DLD-1 | Colon adenocarcinoma | Homo sapiens | CVCL_0248 |
| HT29 | Colon cancer | Mus musculus | CVCL_A8EZ | |
| In-vivo Model | DLD-1 cells were subcutaneously implanted into 4-6 weeks old female nude mice. When tumors reached a size of about 50 mm3, the nude mice were randomly divided into 6 groups. | |||
Full List of Crosstalk(s) between m6A Modification and Epigenetic Regulation Related to This Drug
| In total 9 item(s) under this drug | ||
| Crosstalk ID: M6ACROT03557 | ||
| m6A Regulator | Methyltransferase-like 3 (METTL3) | |
| m6A Target | Translocation protein SEC62 (SEC62) | |
| Epigenetic Regulator | Histone acetyltransferase p300 (P300) | |
| Regulated Target | Histone H3 lysine 27 acetylation (H3K27ac) | |
| Crosstalk relationship | Histone modification → m6A | |
| Disease | Colorectal cancer | |
| Crosstalk ID: M6ACROT03576 | ||
| m6A Regulator | Methyltransferase-like 3 (METTL3) | |
| m6A Target | TNF receptor-associated factor 5 (TRAF5) | |
| Epigenetic Regulator | Histone acetyltransferase p300 (P300) | |
| Regulated Target | Histone H3 lysine 27 acetylation (H3K27ac) | |
| Crosstalk relationship | Histone modification → m6A | |
| Disease | Colorectal cancer | |
| Crosstalk ID: M6ACROT03602 | ||
| m6A Regulator | Methyltransferase-like 3 (METTL3) | |
| m6A Target | Translocation protein SEC62 (SEC62) | |
| Epigenetic Regulator | N-lysine methyltransferase SMYD2 (SMYD2) | |
| Regulated Target | Histone H3 lysine 4 trimethylation (H3K4me3) | |
| Crosstalk relationship | Histone modification → m6A | |
| Disease | Colorectal cancer | |
| Crosstalk ID: M6ACROT03621 | ||
| m6A Regulator | Methyltransferase-like 3 (METTL3) | |
| m6A Target | TNF receptor-associated factor 5 (TRAF5) | |
| Epigenetic Regulator | N-lysine methyltransferase SMYD2 (SMYD2) | |
| Regulated Target | Histone H3 lysine 4 trimethylation (H3K4me3) | |
| Crosstalk relationship | Histone modification → m6A | |
| Disease | Colorectal cancer | |
| Crosstalk ID: M6ACROT03656 | ||
| m6A Regulator | Methyltransferase-like 3 (METTL3) | |
| m6A Target | Poly [ADP-ribose] polymerase 1 (PARP1) | |
| Epigenetic Regulator | Histone-lysine N-methyltransferase EZH2 (EZH2) | |
| Regulated Target | Histone H3 lysine 27 trimethylation (H3K27me3) | |
| Crosstalk relationship | Histone modification → m6A | |
| Disease | Gastric cancer | |
| Crosstalk ID: M6ACROT05220 | ||
| m6A Regulator | Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) | |
| m6A Target | Glucose-6-phosphate dehydrogenase (G6PD) | |
| Epigenetic Regulator | Long intergenic non-protein coding RNA 1615 (LINC01615) | |
| Regulated Target | Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) | |
| Crosstalk relationship | ncRNA → m6A | |
| Disease | Colorectal cancer | |
| Crosstalk ID: M6ACROT06035 | ||
| m6A Regulator | Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) | |
| m6A Target | RNA component of 7SK nuclear ribonucleoprotein (RN7SK) | |
| Epigenetic Regulator | RNA component of 7SK nuclear ribonucleoprotein (RN7SK) | |
| Regulated Target | Cullin 1 (CUL1) | |
| Crosstalk relationship | m6A → ncRNA | |
| Crosstalk ID: M6ACROT06036 | ||
| m6A Regulator | Methyltransferase-like 3 (METTL3) | |
| m6A Target | RNA component of 7SK nuclear ribonucleoprotein (RN7SK) | |
| Epigenetic Regulator | RNA component of 7SK nuclear ribonucleoprotein (RN7SK) | |
| Regulated Target | Cullin 1 (CUL1) | |
| Crosstalk relationship | m6A → ncRNA | |
| Crosstalk ID: M6ACROT06037 | ||
| m6A Regulator | YTH domain-containing protein 2 (YTHDC2) | |
| m6A Target | RNA component of 7SK nuclear ribonucleoprotein (RN7SK) | |
| Epigenetic Regulator | RNA component of 7SK nuclear ribonucleoprotein (RN7SK) | |
| Regulated Target | Cullin 1 (CUL1) | |
| Crosstalk relationship | m6A → ncRNA | |
References
