m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03048
 [1]
Histone modification H3K18la LDHB YTHDF2 Direct Enhancement m6A modification PER1 PER1 YTHDF2 : m6A sites
m6A Modification:
m6A Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
m6A Target Period circadian protein homolog 1 (PER1)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator L-lactate dehydrogenase B chain (LDHB) WRITER View Details
Regulated Target Histone H3 lysine 18 lactylation (H3K18la) View Details
Downstream Gene YTHDF2 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 Here, we show histone lactylation is elevated in tumors and is associated with poor prognosis of ocular melanoma. Target correction of aberrant histone lactylation triggers therapeutic efficacy both in vitro and in vivo. Mechanistically, LDHA/LDHB-mediated Histone H3 lysine 18 lactylation (H3K18la) contributes to tumorigenesis by facilitating YTHDF2 expression. Moreover, YTHDF2 recognizes the m6A modified Period circadian protein homolog 1 (PER1) and TP53 mRNAs and promotes their degradation, which accelerates tumorigenesis of ocular melanoma.
Responsed Disease Melanoma of uvea ICD-11: 2D0Y
 Disease Info 
In-vitro Model
 92-1 [Human uveal melanoma] Uveal melanoma Homo sapiens CVCL_8607
MuM-2B Uveal melanoma Homo sapiens CVCL_3447
OCM-1 Amelanotic melanoma Homo sapiens CVCL_6934
Mel290 Uveal melanoma Homo sapiens CVCL_C304
OMM-1 Uveal melanoma Homo sapiens CVCL_6939
CRMM-1 Conjunctival melanoma Homo sapiens CVCL_M593
CRMM-2 Conjunctival melanoma Homo sapiens CVCL_M594
CM2005.1 Conjunctival melanoma Homo sapiens CVCL_M592
PIG1 Normal Homo sapiens CVCL_S410
HEK293T Normal Homo sapiens CVCL_0063
In-vivo Model Briefly, nude mice were anesthetized by intraperitoneal injection of a ketamine (final concentration: 10 mg/mL) and xylazine (final concentration: 1 mg/mL) mixture (0.01 mL/g mouse weight). Then, the mouse sclera was pre-perforated using a sharp 30-gauge injection needle. Ocular melanoma cells (5 × 105) were injected through the hole made in the choroid by a 33-gauge blunt-end microinjection needle (7803-05, Hamilton, Reno, NV, USA). Then, the infected eyes were treated with ophthalmic bacitracin ointment. All animal experiments were approved by the Animal Care and Use Committee at Shanghai Jiao Tong University School of Medicine.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
2D0Y: Melanoma of uvea 1 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Hepzato Phase 3 [2]
External Link
TTD: DFB62M
References
Ref 1 Histone lactylation drives oncogenesis by facilitating m(6)A reader protein YTHDF2 expression in ocular melanoma. Genome Biol. 2021 Mar 16;22(1):85. doi: 10.1186/s13059-021-02308-z.
Ref 2 ClinicalTrials.gov (NCT05022901) An Open-Label Expanded Access Study of the Melphalan/Hepatic Delivery System (HDS) in Patients With Hepatic Dominant Ocular Melanoma. U.S.National Institutes of Health.