m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03054
 [1]
Histone modification H3K9Ac HDAC METTL14 Indirect Enhancement m6A modification FAT4 FAT4 YTHDF1 : m6A sites
m6A Modification:
m6A Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
m6A Target Protocadherin Fat 4 (FAT4)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Histone Deacetylase (HDAC) ERASER View Details
Regulated Target Histone H3 lysine 9 acetylation (H3K9Ac) View Details
Downstream Gene METTL14 View Details
Crosstalk Relationship Histone modification  →  m6A Enhancement
Crosstalk Mechanism histone modification indirectly regulates m6A modification through downstream signaling pathways
Crosstalk Summary First, we found that ocular melanoma cells presented vulnerability towards HDACis. HDACis triggered the elevation of m6A RNA modification in ocular melanoma. Further studies revealed that METTL14 served as a downstream candidate for HDACis. METTL14 was silenced by the hypo-histone acetylation status, whereas HDACi restored the normal histone acetylation (H3K27ac/Histone H3 lysine 9 acetylation (H3K9ac)) level of METTL14, thereby inducing its expression. Subsequently, METTL14 served as a tumor suppressor by promoting the expression of Protocadherin Fat 4 (FAT4), a tumor suppressor, in a m6A-YTHDF1-dependent manner. Taken together, we found that HDACi restored the histone acetylation level of METTL14 and subsequently elicited METTL14-mediated m6A modification in tumorigenesis.
Responsed Disease Melanoma of uvea ICD-11: 2D0Y
 Disease Info 
In-vitro Model
 Mel290 Uveal melanoma Homo sapiens CVCL_C304
OMM2.3 Uveal melanoma Homo sapiens CVCL_C306
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
MuM-2B Uveal melanoma Homo sapiens CVCL_3447
ARPE-19 Normal Homo sapiens CVCL_0145
A-375 Amelanotic melanoma Homo sapiens CVCL_0132
SK-MEL-28 Cutaneous melanoma Homo sapiens CVCL_0526
PIG1 Normal Homo sapiens CVCL_S410
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 Targeting histone deacetylase suppresses tumor growth through eliciting METTL14-modified m(6) A RNA methylation in ocular melanoma. Cancer Commun (Lond). 2023 Nov;43(11):1185-1206. doi: 10.1002/cac2.12471. Epub 2023 Jul 19.
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.