Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05329
[1]
Non-coding RNA miR-26a-5p METTL14  lncRNA       miRNA   circRNA Direct Inhibition m6A modification NLRP3 NLRP3 METTL14 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 14 (METTL14) WRITER
m6A Target NACHT, LRR and PYD domains-containing protein 3 (NLRP3)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator hsa-miR-26a-5p microRNA View Details
Regulated Target Methyltransferase-like protein 14 (METTL14) View Details
Crosstalk Relationship ncRNA  →  m6A Inhibition
Crosstalk Mechanism ncRNAs directly impacts m6A modification through modulating the expression level of m6A regulator
Crosstalk Summary METTL14 was highly present in NP cells from IVDD patients, which stabilize NACHT, LRR and PYD domains-containing protein 3 (NLRP3) mRNA in an IGFBP2-dependent manner. The elevated NLRP3 levels result in the increase of interleukin 1beta (IL-1beta) and IL-18 levels and trigger pyroptotic NP cell death. Such pathogenic axis could be blocked by hucMSC exosomes, which directly degrade METTL14 through exosomal hsa-miR-26a-5p.
Responsed Disease Intervertebral disc degeneration ICD-11: FA80
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
NACHT, LRR and PYD domains-containing protein 3 (NLRP3) 4 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Dapansutrile Phase 2 [2]
Synonyms
54863-37-5; OLT1177; UNII-2Z03364G96; 2Z03364G96; Dapansutrile [INN]; Dapansutrile [USAN:INN]; Dapansutrile (USAN/INN); 3-Methylsulfonylpropionitrile; 3-methanesulfonylpropanenitrile; 3-methylsulphonyl-propionitrile; SCHEMBL9934796; CHEMBL3989943; LQFRYKBDZNPJSW-UHFFFAOYSA-N; MolPort-008-545-498; ZINC32005410; Propanenitrile, 3-(methylsulfonyl)-; AKOS010140086; D10920; Z2719319073
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MOA Inhibitor
External Link
 Compound Name BMS-986299 Phase 1 [3]
MOA Agonist
External Link
 Compound Name Selnoflast Phase 1 [4]
Synonyms
1-(1-ethylpiperidin-4-yl)sulfonyl-3-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)urea; 1-Ethyl-N-(((1,2,3,5,6,7-hexahydro-S-indacen-4-yl)amino)carbonyl)-4-piperidinesulfonamide; 1-ethyl-N-[(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl]piperidine-4-sulfonamide; 2260969-36-4; 4-Piperidinesulfonamide, 1-ethyl-N-(((1,2,3,5,6,7-hexahydro-S-indacen-4-yl)amino)carbonyl)-; 4-Piperidinesulfonamide,1-ethyl-N-[[(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)amino]carbonyl]-; CHEMBL5095423; CS-0204138; Example 6 [WO2019008025A1]; GTPL12173; HY-132831; MFCD34579587; MS-26540; RG6418; RG-6418; RO7486967; RO-7486967; SCHEMBL20634304; Selnoflast; Selnoflast [INN]; Selnoflast [USAN:INN]; Selnoflast [USAN]; SY347075; T23RPA8WA2; UNII-T23RPA8WA2; WHO 11687
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MOA Inhibitor
External Link
 Compound Name MCC950 Investigative [5]
Synonyms
210826-40-7; MCC-950; CP-456773; CHEMBL3183703; N-[[(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)amino]carbonyl]-4-(1-hydroxy-1-methylethyl)-2-furansulfonamide; MCC 950; DSSTox_RID_82252; DSSTox_CID_27301; DSSTox_GSID_47301; SCHEMBL6521858; GTPL8228; DTXSID2047301; MolPort-042-579-517; EX-A1052; BCP15729; Tox21_300462; BDBM50155926; ZINC34025113; AKOS030238802; SB19010; NCGC00254269-01; NCGC00248064-01; HY-12815; CAS-210826-40-7; 1-[4-(1-Hydroxy-1-methylethyl)-2-furylsulfonyl]-3-[(1,2,3,5,6,7-hexahydro-s-indacene)-4-yl]urea
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MOA Inhibitor
Activity IC50 = 5 nM
External Link
FA80: Intervertebral disc degeneration 3 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Rexlemestrocel-L Phase 3 [6]
Synonyms
MPC-150-M
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External Link
 Compound Name CybroCell Phase 1/2 [7]
External Link
 Compound Name IDCT Phase 1/2 [8]
Synonyms
rebonuputemcel
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External Link
References
Ref 1 Human umbilical cord mesenchymal stem cells deliver exogenous miR-26a-5p via exosomes to inhibit nucleus pulposus cell pyroptosis through METTL14/NLRP3. Mol Med. 2021 Aug 19;27(1):91. doi: 10.1186/s10020-021-00355-7.
Ref 2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 3 National Cancer Institute Drug Dictionary (drug name BMS-986299).
Ref 4 Clinical pipeline report, company report or official report of Roche
Ref 5 A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat Med. 2015 Mar;21(3):248-55.
Ref 6 ClinicalTrials.gov (NCT02412735) Placebo-controlled Study to Evaluate Rexlemestrocel-L Alone or Combined With Hyaluronic Acid in Subjects With Chronic Low Back Pain (MSB-DR003). U.S. National Institutes of Health.
Ref 7 Clinical pipeline report, company report or official report of FibroGenesis.
Ref 8 ClinicalTrials.gov (NCT03955315) Study to Evaluate the Safety and Preliminary Efficacy of IDCT, a Treatment for Symptomatic Lumbar Disc Degeneration. U.S. National Institutes of Health.