m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03527
 [1], [2]
Histone modification H3K4me3 WDR5 METTL3 Direct Enhancement m6A modification LINC00426 LINC00426 METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target long intergenic non-protein coding RNA 426 (LINC00426)
 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. METIL3 is believed to enhance the expression of Long intergenic non-protein coding RNA 426 (LINC00426) through m6A methylation modification.The LINC00426/miR-200a-3p/ZEB1 axis plays a crucial role in regulating E-cadherin, N-cadherin and vimentin during EMT in CC.Overexpression of LINC00426 in CC cells caused resistance to Cisplatin and Bleomycin, but sensitivity to imatinib.
Responsed Disease Cervical cancer ICD-11: 2C77
 Disease Info 
Responsed Drug Bleomycin
 Drug Info 
In-vitro Model
 HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
C-33 A Cervical squamous cell carcinoma Homo sapiens CVCL_1094
SiHa Cervical squamous cell carcinoma Homo sapiens CVCL_0032
In-vivo Model HeLa cells were stably transfected with LINC00426 overexpression lentivirus. Subsequently, for subcutaneously implanted tumor model, mice were randomly divided into two groups, and cells (1 × 107/100 μ l) mixed with the same volume of matrix gel were injected subcutaneously into the right abdomen of mice. One month later the mice were executed and the tumors were stripped and weighed, measured for volume, and used for further analysis. For tumor metastasis assay, mice were randomly grouped, and 5 × 105/100 μ l HeLa cells transfected with NC and LINC00426 overexpression lentivirus were intravenously injected into the tail vein of BALB/c nude mice which were sacrificed after 1 month.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
WD repeat-containing protein 5 (WDR5) 1 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name OICR-9429 Investigative [3]
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 LINC00426, a novel m(6)A-regulated long non-coding RNA, induces EMT in cervical cancer by binding to ZEB1. Cell Signal. 2023 Sep;109:110788. doi: 10.1016/j.cellsig.2023.110788. Epub 2023 Jun 29.
Ref 3 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).