General Information of the Drug (ID: M6ADRUG0086)
Name
Glucocorticoid
Status Investigative [1]
TTD Drug ID
D05TNY
Full List of m6A Targets Related to This Drug
Ubiquitin carboxyl-terminal hydrolase 1 (USP1)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary ALKBH5 and Ubiquitin carboxyl-terminal hydrolase 1 (USP1) were upregulated in T-cell acute lymphoblastic leukemia, and ALKBH5-mediated m6A modification increased USP1 and Aurora B expression. Silencing USP1 increased CEM-C1 cell sensitivity to dexamethasone, reduced cell invasion, promoted cell apoptosis, and ameliorated glucocorticoid receptor (GR) expression.
Responsed Disease Mature T-cell lymphoma ICD-11: 2A90
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
Target Regulation Up regulation
Cell Process Cell apoptosis
In-vitro Model CEM/C1 T acute lymphoblastic leukemia Homo sapiens CVCL_3496
CCRF-CEM C7 T acute lymphoblastic leukemia Homo sapiens CVCL_6825
HEK293T Normal Homo sapiens CVCL_0063
In-vivo Model Adult male C57BL/6J mice (weighting 18-25 g) were obtained from Laboratory Animal Center, Zhengzhou University. Mice were subcutaneously injected with 1 × 107 CEM-C1 cells for tumorigenesis and randomly divided into four group: control group; control + Dex; sh-RNA + Dex; sh-USP1 + Dex. Mice treatment with Dex were intraperitoneally injected with 8 mg/kg Dex every day for 10 consecutive days after tumor growth and mice treatment with sh-RNA or sh-USP1 were injected intravenously with 2 mg/Kg sh-RNA or USP1 sh-RNA. The control group of mice were injected with the same volume of normal saline. After the treatment of each group, the mice were housed and fed in a room with an ambient temperature of 25℃, and the survival time, weight of the mice, and tumor weight were recorded. When rats were sacrificed, tissues were harvested for Western blot analysis.
References
Ref 1 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
Ref 2 ALKBH5-mediated m6A-demethylation of USP1 regulated T-cell acute lymphoblastic leukemia cell glucocorticoid resistance by Aurora B. Mol Carcinog. 2021 Sep;60(9):644-657. doi: 10.1002/mc.23330. Epub 2021 Jun 25.