Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT00417
[1], [2], [3], [4], [5], [6], [7]
RNA modification MIR21 MIR21 ADARB1 Methylation : modification sites Indirect Inhibition m6A modification FOXM1 FOXM1 ALKBH5 Demethylation : m6A sites
m6A Modification:
m6A Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
m6A Target Forkhead box protein M1 (FOXM1)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type RNA modification (RNAMod)  >> Adenosine-to-Inosine editing (A-to-I)
Epigenetic Regulator Double-stranded RNA-specific editase 1 (ADARB1) WRITER View Details
Regulated Target MicroRNA 21 (MIR21) View Details
Crosstalk Relationship A-to-I  →  m6A Inhibition
Crosstalk Mechanism RNA modification indirectly impacts m6A modification through downstream signaling pathways
Crosstalk Summary ADARB1 interacts with MicroRNA 21 (MIR21), increasing it's A-to-I level and inhibiting its physical interaction with Forkhead box protein M1 (FOXM1), which was regulated by ALKBH5-mediated m6A modification.
In-vitro Model
GSC17 Glioblastoma Homo sapiens CVCL_DR57
GSC11 Glioblastoma Homo sapiens CVCL_DR55
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
HEK293T Normal Homo sapiens CVCL_0063
C918 Uveal melanoma Homo sapiens CVCL_8471
U-118MG Astrocytoma Homo sapiens CVCL_0633
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Forkhead box protein M1 (FOXM1) 1 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name (D-Arg)(9)-p19(ARF) 26-44 peptide Investigative [8]
MOA Inhibitor
External Link
References
Ref 1 m(6)A Demethylase ALKBH5 Maintains Tumorigenicity of Glioblastoma Stem-like Cells by Sustaining FOXM1 Expression and Cell Proliferation Program. Cancer Cell. 2017 Apr 10;31(4):591-606.e6. doi: 10.1016/j.ccell.2017.02.013. Epub 2017 Mar 23.
Ref 2 ALKBH5-m(6)A-FOXM1 signaling axis promotes proliferation and invasion of lung adenocarcinoma cells under intermittent hypoxia. Biochem Biophys Res Commun. 2020 Jan 8;521(2):499-506. doi: 10.1016/j.bbrc.2019.10.145. Epub 2019 Oct 31.
Ref 3 DDX3 modulates cisplatin resistance in OSCC through ALKBH5-mediated m(6)A-demethylation of FOXM1 and NANOG. Apoptosis. 2020 Apr;25(3-4):233-246. doi: 10.1007/s10495-020-01591-8.
Ref 4 ALKBH5-mediated m(6)A demethylation of FOXM1 mRNA promotes progression of uveal melanoma. Aging (Albany NY). 2021 Jan 10;13(3):4045-4062. doi: 10.18632/aging.202371. Epub 2021 Jan 10.
Ref 5 Modulation of microRNA editing, expression and processing by ADAR2 deaminase in glioblastoma. Genome Biol. 2015 Jan 13;16(1):5. doi: 10.1186/s13059-014-0575-z.
Ref 6 The Role of ADAR1 and ADAR2 in the Regulation of miRNA-21 in Idiopathic Pulmonary Fibrosis. Lung. 2018 Aug;196(4):393-400. doi: 10.1007/s00408-018-0115-9. Epub 2018 Apr 10.
Ref 7 microRNA-21 regulates the proliferation of placental cells via FOXM1 in preeclampsia. Exp Ther Med. 2020 Sep;20(3):1871-1878. doi: 10.3892/etm.2020.8930. Epub 2020 Jun 24.
Ref 8 Foxm1b transcription factor is essential for development of hepatocellular carcinomas and is negatively regulated by the p19ARF tumor suppressor. Genes Dev. 2004 Apr 1;18(7):830-50. doi: 10.1101/gad.1200704.