Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05558
[1]
m6A modification MIR150 MIR150 METTL3 Methylation : m6A sites Direct Enhancement Non-coding RNA miR-150 BDNF  lncRNA       miRNA   circRNA
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
m6A Target microRNA 150 (MIR150)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator MicroRNA 150 (MIR150) microRNA View Details
Regulated Target Neurotrophic factor BDNF precursor form (BDNF) View Details
Crosstalk Relationship m6A  →  ncRNA Enhancement
Crosstalk Mechanism m6A regulators directly modulate the functionality of ncRNAs through specific targeting ncRNA
Crosstalk Summary Enhanced METTL3 promoted the m6A methylation in total RNAs and inhibited neuropathic pain (NP) progression. Mechanistically, METTL3 accelerated microRNA 150 (MIR150) maturation via mediating m6A methylation of primiR-150 at locus 498, cooperating with the "m6A reader" YTHDF2. Therefore, the METTL3/miR-150/Neurotrophic factor BDNF precursor form (BDNF) pathway is a promising therapeutic target for NP patients.
Responsed Disease Neuropathic pain ICD-11: 8E43.0
In-vitro Model
RN-sc (The rat neuron cell line RN-sc was purchased from ScienCell)
In-vivo Model Based on our study design, the enrolled animals were blindingly grouped and received the following treatments: (1)Sham-NC vectors, (2)Sham-sh-METTL3, (3)Sham-sh-METTL3 + miR-150, (4)Sham-sh-METTL3 + Lv-YTHDF2, (5)Sham-sh-METTL3 + sh-BDNF, (6)Sham-anti-miR150, (7)Sham-anti-miR150+sh-BDNF, (8)SNI-Lv-METTL3, (9)SNI-Lv-METTL3 + anti-miR-150, (10)SNI-Lv-METTL3 + sh-YTHDF2, (11)SNI-Lv-METTL3 + Lv-BDNF, (12)SNI-miR150, (13)SNI-miR150+Lv-BDNF. The pain behaviors were detected in the respective time points and the expressions of METTL3 and miR-150 were determined at day 14 after the rats were sacrificed.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Neurotrophic factor BDNF precursor form (BDNF) 1 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name PYM-50028 Phase 2 [2]
Synonyms
Cogane; Smilagenin; P-58; P-63
    Click to Show/Hide
MOA Agonist
External Link
8E43: Pain disorders 1 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name FMX104 Phase 2 [3]
External Link
References
Ref 1 METTL3 suppresses neuropathic pain via modulating N6-methyladenosine-dependent primary miR-150 processing. Cell Death Discov. 2022 Feb 24;8(1):80. doi: 10.1038/s41420-022-00880-2.
Ref 2 PYM50028, a novel, orally active, nonpeptide neurotrophic factor inducer, prevents and reverses neuronal damage induced by MPP+ in mesencephalic neurons and by MPTP in a mouse model of Parkinson's disease. FASEB J. 2008 Jul;22(7):2488-97.
Ref 3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)