Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05204
[1]
Non-coding RNA FTO-IT1 RBM15  lncRNA       miRNA   circRNA Direct Inhibition m6A modification TP53INP1 TP53INP1 RBM15 Methylation : m6A sites
m6A Modification:
m6A Regulator RNA-binding motif protein 15 (RBM15) WRITER
m6A Target Tumor protein p53-inducible nuclear protein 1 (TP53INP1)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator FTO intronic transcript 1 (FTO-IT1) LncRNA View Details
Regulated Target RNA binding motif protein 15 (RBM15) View Details
Crosstalk Relationship ncRNA  →  m6A Inhibition
Crosstalk Mechanism ncRNAs directly impacts m6A modification through recruiting m6A regulator
Crosstalk Summary m6A RIP-seq analysis revealed that FTO-IT1 knockout increased mRNA m6A methylation of a subset of p53 transcriptional target genes (e.g., FAS, Tumor protein p53-inducible nuclear protein 1 (TP53INP1), and SESN2) and induced PCa cell cycle arrest and apoptosis. FTO-IT1 directly binds RBM15 and inhibits RBM15 binding, m6A methylation, and stability of p53 target mRNAs.
In-vitro Model
HEK293T Normal Homo sapiens CVCL_0063
22Rv1 Prostate carcinoma Homo sapiens CVCL_1045
LNCaP C4-2 Prostate carcinoma Homo sapiens CVCL_4782
PC-3 Prostate carcinoma Homo sapiens CVCL_0035
LNCaP Prostate carcinoma Homo sapiens CVCL_0395
LAPC-4 Prostate carcinoma Homo sapiens CVCL_4744
In-vivo Model 5 × 106 of mock KO or FTO-IT1 KO C4-2R cells were mixed with Matrigel (50 μ l of PBS plus 50 μ l of Matrigel (BD Biosciences)) and injected subcutaneously into mice. For 22Rv1 xenografts, 5 × 106 of cells were mixed with Matrigel (50 μ l of PBS plus 50 μ l of Matrigel (BD Biosciences)) and injected subcutaneously into mice.
References
Ref 1 A lncRNA from the FTO locus acts as a suppressor of the m(6)A writer complex and p53 tumor suppression signaling. Mol Cell. 2023 Aug 3;83(15):2692-2708.e7. doi: 10.1016/j.molcel.2023.06.024. Epub 2023 Jul 20.