m6A-centered Crosstalk Information
Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
| Crosstalk ID |
M6ACROT05289
|
[1], [2] | |||
Non-coding RNA
miR-34a-5p
IGF2BP2
lncRNA miRNA circRNA
Direct
Inhibition
m6A modification
GNAS-AS1
GNAS-AS1
IGF2BP2
 : m6A sites
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| m6A Modification: | |||||
|---|---|---|---|---|---|
| m6A Regulator | Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) | READER | |||
| m6A Target | GNAS antisense RNA 1 (GNAS-AS1) | ||||
| Epigenetic Regulation that have Cross-talk with This m6A Modification: | |||||
| Epigenetic Regulation Type | Non-coding RNA (ncRNA) | ||||
| Epigenetic Regulator | hsa-miR-34a-5p | microRNA | View Details | ||
| Regulated Target | Insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) | View Details | |||
| Crosstalk Relationship | ncRNA → m6A | Inhibition | |||
| Crosstalk Mechanism | ncRNAs directly impacts m6A modification through recruiting m6A regulator | ||||
| Crosstalk Summary | Chidamide inhibited glycolysis in AML by repressing WTAP-mediated GNAS antisense RNA 1 (GNAS-AS1) m6A modification and then regulating the hsa-miR-34a-5p/IGF2BP2 axis.Chidamide inhibits cell glycolysis in acute myeloid leukemia by decreasing N6-methyladenosine-related GNAS-AS1.Chidamide treatment suppressed WT1-associated protein (WTAP)-mediated RNA m6A modification of GNAS-AS1. Chidamide downregulated GNAS-AS1 to inhibit glycolysis in AML cells. GNAS-AS1 targeted miR-34a-5p to promote insulin-like growth factor 2 mRNA-binding protein (IGF2BP2) expression. IGF2BP2 inhibition reversed the promoting effect of miR-34a-5p knockdown on glycolysis and RhoA/ROCK pathway in Chidamide-treated cells. GNAS-AS1 overexpression abolished the inhibitory effect of Chidamide on AML tumorigenesis in vivo by modulating the RhoA/ROCK pathway. | ||||
| Responsed Disease | Breast cancer | ICD-11: 2C60 | |||
| Responsed Drug | Tamoxifen | ||||
| Pathway Response | TGF-beta signaling pathway | hsa04350 | |||
| Cell Process | Endocrine-resistance | ||||
In-vitro Model |
MCF-7 | Invasive breast carcinoma | Homo sapiens | CVCL_0031 | |
| MCF7/LCC9 | Invasive breast carcinoma | Homo sapiens | CVCL_DP52 | ||
| In-vivo Model | Subcutaneous tumorigenesis was induced in mice by subcutaneous transplantation of 1 × 106 HL-60 cells. To stably overexpress GNAS-AS1, lentivirus-packaged OE-GNAS-AS1 (1 × 108 plaque-forming units). When the tumor volume reached 150-200 mm3, mice in the control group were orally treated with 1% DMSO (containing 0.2% carboxymethylcellulose and 0.1% Tween 80). Mice in the Chidamide, Chidamide + OE-NC, and Chidamide + OE-GNAS-AS1 groups were orally treated with Chidamide (25 mg/kg body weight, formulated with 1% DMSO containing 0.2% carboxymethylcellulose and 0.1% Tween 80). All treatments were repeated three times a week and for two weeks. Tumor volume was recorded every 5 days. | ||||
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
| 2C60: Breast cancer | 2 Compound(s) Regulating the Disease | Click to Show/Hide the Full List | ||
 Compound Name |
Entrectinib | Approved | [3] | |
|---|---|---|---|---|
| Synonyms |
1108743-60-7; RXDX-101; UNII-L5ORF0AN1I; Entrectinib (RXDX-101); L5ORF0AN1I; Benzamide, N-[5-[(3,5-difluorophenyl)methyl]-1H-indazol-3-yl]-4-(4-methyl-1-piperazinyl)-2-[(tetrahydro-2H-pyran-4-yl)amino]-; Benzamide, N-(5-((3,5-difluorophenyl)methyl)-1H-indazol-3-yl)-4-(4-methyl-1-piperazinyl)-2-((tetrahydro-2H-pyran-4-yl)amino)-; Entrectinib [USAN:INN]; YMX; Kinome_2659; Entrectinib(rxdx-101); Entrectinib (USAN/INN); SCHEMBL3512601; GTPL8290; CHEMBL1983268; KS-00000TSK
Click to Show/Hide
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| External Link | ||||
| Compound Name |
Everolimus | Approved | [4] | |
| External Link | ||||
References