Cross-Talk between Oxidative Stress and m⁶A RNA Methylation in Cancer

Table 3

m⁶A RNA methylation regulates oxidative stress in cancer.

m^6A enzyme	Change of m^6A modification	ROS levels	Cancer type	Mechanism	Biofunction in cancer	References
METTL3; ALKBH5	m^6A level↑	↑	Breast cancer	METTL3 enhances AK4 expression, increase the level of ROS in breast cancer cells and activate p38 Kinase	Promoting the resistance of breast cancer to Tamoxifen	[226]
METTL3	Unknown	↑	Colorectal cancer	METTL3 facilitates the processing of miR-483, miR-676, and miR-877 which regulating the expression of mitochondrial related ETC genes	Promoting cancer growth and progression	[225]
METTL3; METTL14	Unknown	↓	Colon carcinoma	METTL3/METTL14 catalyzes the m^6A methylation of p21 and enhances p21 expression leading to elevated expression of Nrf2	Inducing cell senescence	[208, 229]
FTO	Unknown	↑	Clear cell renal cell carcinoma	FTO increases stability and translation of PGC-1α mRNA thereby resulting in oxidative stress	Inducing ROS production and suppressing tumor growth	[227]
YTHDF1	YTHDF1↓	↓	Nonsmall cell lung cancer	Knockdown of YTHDF1 reduces the translation of keap, upregulates Nrf2 and its downstream antioxidant in response of cisplatin-induced ROS	Adapting to oxidative stress; Inducing cisplatin resistance in nonsmall cell lung cancer	[215]
METTL3; YTHDF2	METTL3↑; SUMOylation of YTHDF2	↑	Lung adenocarcinoma	YTHDF2 can be SUMOylated at K571 in hypoxia or oxidative stress condition	Promoting mRNA degradation and cancer progression	[21]
YTHDC2	Unknown	↑	Lung adenocarcinoma	YTHDC2 regulates SLC7A11 mRNA decay, which leads to the inhibition system XC(-) function, thus impairing the antioxidant function	Inhibiting tumorigenesis	[233]