General Information of the Disease (ID: M6ADIS0174)
Name
Gastrointestinal stromal tumor
ICD
ICD-11: 2B5B
Full List of Target Gene(s) of This m6A-centered Disease Response
Multidrug resistance-associated protein 1 (MRP1/ABCC1)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary METTL3, and the YTHDF1/eEF-1 complex mediate the translation of Multidrug resistance-associated protein 1 (MRP1/ABCC1) mRNA in an m6A-dependent manner to regulate the intracellular concentration of imatinib and drug resistance of gastrointestinal stromal tumor (GIST).
Responsed Disease Gastrointestinal stromal tumour [ICD-11: 2B5B]
Responsed Drug Imatinib Approved
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
In-vitro Model GIST-T1 Gastrointestinal stromal tumor Homo sapiens CVCL_4976
GIST882 Gastrointestinal stromal tumor Homo sapiens CVCL_7044
In-vivo Model For tumor growth assay, 4 × 106 logarithmically growing GIST cells were transfected with T1S-vector, T1S-METTL3, 882S-vector, or 882S-METTL3 constructs, and subcutaneously injected in 100 ul of PBS into the flank of female nude mice(4-week-old). Mice were then randomly divided into 8 groups (n = 5 in each group): (1) injected with T1S-vector-harboring cells, and treated with imatinib (600 mg/l in drinking water); (2) injected with T1S-vector-harboring cells, and treated with imatinib (600 mg/l in drinking water) and MRP1 inhibitor (100 mg/l in drinking water); (3) injected with T1S-METTL3-harboring cells, and treated with imatinib (600 mg/l in drinking water); (4) injected with T1S-METTL3-harboring cells, and treated with imatinib (600 mg/l in drinking water) and MRP1 inhibitor (100 mg/l in drinking water); (5) injected with 882S-vector-harboring cells and treated with imatinib (600 mg/l in drinking water); (6) injected with 882S-vector-harboring cells, and treated with imatinib (600 mg/l in drinking water) and MRP1 inhibitor (100 mg/l in drinking water); (7) injected with 882S-METTL3-harboring cells, and treated with imatinib (600 mg/l in drinking water); and (8) injected with 882S-METTL3-harboring cells, and treated with imatinib (600 mg/l in drinking water) and MRP1 inhibitor (100 mg/l in drinking water).
Full List of Crosstalk(s) between m6A Modification and Epigenetic Regulation Related to This Disease
In total 1 item(s) under this disease
Crosstalk ID: M6ACROT05732
m6A Regulator Methyltransferase-like 3 (METTL3)
m6A Target microRNA 675 (MIR675)
Epigenetic Regulator MicroRNA 675 (MIR675)
Regulated Target myosin phosphatase targeting protein 1 (MYPT1)
Crosstalk relationship m6A → ncRNA
References
Ref 1 N(6)-methyladenosine modification regulates imatinib resistance of gastrointestinal stromal tumor by enhancing the expression of multidrug transporter MRP1. Cancer Lett. 2022 Apr 1;530:85-99. doi: 10.1016/j.canlet.2022.01.008. Epub 2022 Jan 13.
Ref 2 ClinicalTrials.gov (NCT03473457) CAR-T Cells Therapy in Relapsed/Refractory Acute Myeloid Leukemia
Ref 3 A RNA antagonist of hypoxia-inducible factor-1alpha, EZN-2968, inhibits tumor cell growth. Mol Cancer Ther. 2008 Nov;7(11):3598-608. doi: 10.1158/1535-7163.MCT-08-0510. Epub 2008 Oct 30.