m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03520
 [1], [2]
Histone modification H3K4me3 WDR5 METTL3 Direct Enhancement m6A modification HK2 HK2 METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Hexokinase-2 (HK2)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator WD repeat-containing protein 5 (WDR5) WRITER View Details
Regulated Target Histone H3 lysine 4 trimethylation (H3K4me3) View Details
Downstream Gene METTL3 View Details
Crosstalk Relationship Histone modification  →  m6A Enhancement
Crosstalk Mechanism histone modification directly impacts m6A modification through modulating the level of m6A regulator
Crosstalk Summary The transcription factor ETS1 recruited P300 and WDR5 which separately mediated H3K27ac and Histone H3 lysine 4 trimethylation (H3K4me3) histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. METTL3 enhanced the Hexokinase-2 (HK2) stability through YTHDF1-mediated m6A modification, thereby promoting the Warburg effect of CC, which promotes a novel insight for the CC treatment.
Responsed Disease Cervical cancer ICD-11: 2C77
 Disease Info 
Pathway Response Glycolysis / Gluconeogenesis hsa00010), Central carbon metabolism in cancer
Cell Process Glycolysis
In-vitro Model
 Ca Ski Cervical squamous cell carcinoma Homo sapiens CVCL_1100
SiHa Cervical squamous cell carcinoma Homo sapiens CVCL_0032
C-33 A Cervical squamous cell carcinoma Homo sapiens CVCL_1094
HT-3 Cervical carcinoma Homo sapiens CVCL_1293
Ca Ski Cervical squamous cell carcinoma Homo sapiens CVCL_1100
SiHa Cervical squamous cell carcinoma Homo sapiens CVCL_0032
C-33 A Cervical squamous cell carcinoma Homo sapiens CVCL_1094
HT-3 Cervical carcinoma Homo sapiens CVCL_1293
In-vivo Model Five-week-old male nude BALB/C mice were applied for this animal studies and fed with certified standard diet and tap water ad libitum in a light/dark cycle of 12 h on/12 h off.The assay was performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Stable transfection of METTL3 knockdown (sh-METTL3) or negative control (sh-blank) in SiHa cells (5 × 106 cells per 0.1 mL) were injected into the flank of mice.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Hexokinase-2 (HK2) 1 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name VDA-1102 Phase 2 [3]
MOA Modulator
External Link
TTD: D06QBX
WD repeat-containing protein 5 (WDR5) 1 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name OICR-9429 Investigative [4]
Synonyms
1801787-56-3; OICR9429; CHEMBL3798846; N-(4-(4-Methylpiperazin-1-Yl)-3'-(Morpholinomethyl)-[1,1'-Biphenyl]-3-Yl)-6-Oxo-4-(Trifluoromethyl)-1,6-Dihydropyridine-3-Carboxamide; N-[2-(4-methylpiperazin-1-yl)-5-[3-(morpholin-4-ylmethyl)phenyl]phenyl]-6-oxo-4-(trifluoromethyl)-1,6-dihydropyridine-3-carboxamide; GTPL8231; OICR 9429; MolPort-039-101-294; EX-A2417; BCP18185; BDBM50164794; s7833; AKOS025147341; ZINC231558892; SB19642; CS-5776; NCGC00371263-02; AK468854; HY-16993; J3.618.049H
    Click to Show/Hide
MOA Antagonist
External Link
CID: 91623360
TTD: D0XI3W
References
Ref 1 METTL3 potentiates progression of cervical cancer by suppressing ER stress via regulating m6A modification of TXNDC5 mRNA. Oncogene. 2022 Sep;41(39):4420-4432. doi: 10.1038/s41388-022-02435-2. Epub 2022 Aug 20.
Ref 2 N(6)-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification. Cell Death Dis. 2020 Oct 24;11(10):911. doi: 10.1038/s41419-020-03071-y.
Ref 3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 4 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. (Target id: 2831).