Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT00014
[1]
RNA modification GPX4 GPX4 NSUN5 Methylation : modification sites Direct Enhancement m6A modification GPX4 GPX4 RBM15B Methylation : m6A sites
m6A Modification:
m6A Regulator RNA-binding motif protein 15B (RBM15B) WRITER
m6A Target Phospholipid hydroperoxide glutathione peroxidase GPX4 (GPX4)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type RNA modification (RNAMod)  >> 5-methylcytidine (m5C)
Epigenetic Regulator 28S rRNA (cytosine-C(5))-methyltransferase (NSUN5) WRITER View Details
Regulated Target Phospholipid hydroperoxide glutathione peroxidase GPX4 (GPX4) View Details
Crosstalk Relationship m5C  →  m6A Enhancement
Crosstalk Mechanism RNA modification directly impacts m6A modification through recruiting m6A regulator and targeting the shared RNA
Crosstalk Summary RBM15B- and IGFBP2-mediated N6-methyladenosine (m6A) modification and NSUN5-mediated 5-methylcytosine (m5C) modification of Phospholipid hydroperoxide glutathione peroxidase GPX4 (GPX4) facilitated anticancer immunity via activation of cyclic GMP-AMP synthase (cGAS)-stimulator of interferon (STING) signaling by maintaining redox homeostasis in COAD.
Responsed Disease Colon cancer ICD-11: 2B90
Pathway Response cGAS-STING signaling pathway hsa:00395
Cell Process Immune cells infiltration
In-vitro Model
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
HT29 Colon cancer Mus musculus CVCL_A8EZ
In-vivo Model To develop the syngeneic model, 1 × 106 MC38-Ctrl or MC38-Gpx4KD cells were injected subcutaneously into the right flank of C57BL/6 mice, respectively. These two groups of mice were randomly and blindly allocated into separate groups 12 days after cell injection. Subsequently, either an anti-PD-1 antibody (5 mg/kg per mouse) or an IgG isotype was administered intraperitoneally every 2 days until the conclusion of the observation period.
References
Ref 1 m6A and m5C modification of GPX4 facilitates anticancer immunity via STING activation. Cell Death Dis. 2023 Dec 8;14(12):809. doi: 10.1038/s41419-023-06241-w.