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

Table 2

Effects of oxidative stress in cancers.

Cancer type	Gene involved	Function of ROS	Description	References
Acute myeloid leukemia	TIGAR	Tumor suppressor	Knockdown of TIGAR promoting ROS-mediated apoptosis and antiproliferation	[311]
	NOX	Tumor promoter	Activation of NOX increases extracellular ROS level promoting the proliferation of acute myeloid leukemia blasts	[312]
Breast cancer	p53	Tumor suppressor	p53 activation induced by ROS can promote necrosis and apoptosis of cancer cells	[313]
	SOD2	Tumor promoter	Upregulation of SOD2 induces elevated ROS to sustain AMPK-activated signal to promote aerobic glycolysis and malignant transformation	[314]
	ZEB1; GPX4	Tumor promoter	ZEB1 inhibits transcription of GPX4, increases ROS accumulation and EMT, which promote breast cancer progression	[315]
Colorectal cancer	HIF-2α	Tumor suppressor	Activated HIF-2α induces ROS production by an iron-dependent pathway which led colorectal cancer cell death	[316]
	ANGPTL4; NOX4	Tumor promoter	ANGPTL4/NOX4 axis maintains the metastatic ability of colorectal cancer cells via increasing ROS, MMP1, and MMP9 levels	[317]
Glioblastoma	PRDX3	Tumor suppressor	Prohibitin maintains the stability of PRDX3 to reduce the production of ROS, maintain glioblastoma stemness and promote the resistance of gliomas stem-like cells to radiotherapy	[318]
	TRAP1; SIRT3	Tumor suppressor	TRAP1 cooperate with SIRT3 to reduce ROS production and promotes stress adaptation of glioblastoma cancer stem cells	[319]
Gastric cancer	NNT	Tumor suppressor	NNT deficiency can significantly reduce NADPH and significantly induce ROS production and apoptosis under stress.	[320]
	GRIM-19; Nrf2	Tumor promoter	GRIM-19 deficiency accelerates gastric cancer metastasis via abnormal oxidative stress and ROS-driven Nrf2 activation	[321]
Hepatocellular carcinoma	UBQLN1; PGC1β	Tumor suppressor	Elevated expression of UBQLN1 induces PGC1β degradation to promote sorafenib resistance of hepatocellular carcinoma cells by reducing mitochondrial ROS production	[322]
	PKCλ/ι; Nrf2	Tumor promoter	Loss of PKCλ/ι induces ROS generation promoting hepatocellular carcinoma in a Nrf2-dependent manner	[323]
Lung cancer	IL-15; mTOR	Tumor promoter	NK cells activate thioredoxin system through IL-15/mTOR axis to adapt to high ROS level in tumor microenvironment	[324]
	AK4; HIF-1α	Tumor promoter	Upregulation of AK4 enhances expression of HIF-1α through increasing ROS production, and then EMT was induced in hypoxia condition	[325]
	AIM2; MAPK/ERK; MFN2	Tumor promoter	Knockdown of AIM2 upregulates MFN2 and enhances the mitochondrial fusion, resulting in the reduction of mitochondrial ROS production, which in turn induces the inactivation of the MAPK/ERK pathway and hinders the progress of non-small cell lung cancer	[326]
	Nestin; Keap1; Nrf2;	Tumor suppressor	Nestin competed with Nrf2 for binding to Keap1, leading to Nrf2 escape and downstream antioxidant gene expression, which promotes the resistance of NSCLC to oxidative stress	[327]
Melanoma	ANGPT2	Tumor suppressor	Silence of Angpt2 expression significantly increases the level of intracellular ROS and activation of downstream MAPK pathway, thus resulting in the metastatic colonization of melanoma	[328]
	Akt	Tumor promoter	Akt overexpression can induce the expression of NOX4, increase the level of ROS, increase the expression of VEGF, increase angiogenesis, and promote the aerobic glycolysis of melanoma cells	[329]
Ovarian cancer	RAD51	Tumor promoter	Loss of RAD51 accelerates mitochondrial ROS accumulation and DNA damage which can be weakened by treatment of antioxidant N-acetylcysteine	[330]
Pancreas cancer	UCP2; Akt; mTOR	Tumor suppressor	Inhibition of UCP2 plays an anticarcinogenic role in pancreatic adenocarcinoma cells via activating ROS/Akt/mTOR axis	[331]
Renal cell carcinoma	TAZ; EMP1; NOX4;	Tumor suppressor	Nuclear translocation of TAZ upregulates EMP1 expression, thereby increasing the mRNA level of NOX4 and inducing ferroptosis of renal cell carcinoma cells via elevated lipid ROS	[332]