Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05346
[1], [2]
Non-coding RNA MiR-155 FTO  lncRNA       miRNA   circRNA Direct Inhibition m6A modification PPARGC1A PPARGC1A FTO Demethylation : m6A sites
m6A Modification:
m6A Regulator Fat mass and obesity-associated protein (FTO) ERASER
m6A Target PPAR-gamma coactivator 1-alpha (PGC-1a/PPARGC1A)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator MicroRNA 155 (MIR155) microRNA View Details
Regulated Target FTO alpha-ketoglutarate dependent dioxygenase (FTO) View Details
Crosstalk Relationship ncRNA  →  m6A Inhibition
Crosstalk Mechanism ncRNAs directly impacts m6A modification through modulating the expression level of m6A regulator
Crosstalk Summary MIR155 regulates m6A level and cell progression by targeting FTO in clear cell renal cell carcinoma.FTO plays a critical anti-tumorigenic role in Clear Cell Renal Cell Carcinoma.Restored expression of FTO, through reducing m6A levels in mRNA transcripts of its critical target gene PPAR-gamma coactivator 1-alpha (PGC-1a/PPARGC1A), increases mitochondrial content, ROS production and oxidative damage, with the most important effect of repressed tumour growth.
Responsed Disease Clear cell renal cell carcinoma ICD-11: XH46F1
Pathway Response Apoptosis hsa04210
Cell Process Oxidative stress
ROS production
In-vitro Model
HEK293T Normal Homo sapiens CVCL_0063
786-O Renal cell carcinoma Homo sapiens CVCL_1051
769-P Renal cell carcinoma Homo sapiens CVCL_1050
In-vivo Model Five- to 6-week-old male athymic nude mice purchased by Charles River were used for the xenograft model. 769-P cells stably expressing Ctrl, FTO and FTO-mut were trypsinized and washed twice to thrice with standardized PBS, and then, 5 × 106 cells in 100 uL of PBS was subcutaneously injected into the flanks of the mice (five mice per group). Mice were monitored twice every week for tumour growth, and tumour diameters were measured using a caliper.
References
Ref 1 MiR-155 regulates m(6)A level and cell progression by targeting FTO in clear cell renal cell carcinoma. Cell Signal. 2022 Mar;91:110217. doi: 10.1016/j.cellsig.2021.110217. Epub 2021 Dec 16.
Ref 2 N6-methyladenosine demethylase FTO suppresses clear cell renal cell carcinoma through a novel FTO-PGC-1Alpha signalling axis. J Cell Mol Med. 2019 Mar;23(3):2163-2173. doi: 10.1111/jcmm.14128. Epub 2019 Jan 16.