TABLE 2.

The functional roles of RNA m⁶A modification in various types of human disease.

Age-related disease	Organism	Role in disease	m6A regulator	Functional in disease	Ref
Cancer:
Respiratory neoplasms
Lung cancer	Clinical Samples; cells	Oncogene	METTL3; FTO; YTHDF1/2; IGF2BP1	Promote LC growth and progress; induce invasion and metastasis of NSCLC	(Lin et al., 2016; Chen et al., 2020a), (Liu et al., 2018a; Chen et al., 2018; Müller et al., 2019)
	Cells	Suppressor	ALKBH5	Inhibits tumor growth and metastasis	Jin et al. (2020)
Nasopharyngeal carcinoma	Cells	Oncogene	METTL3	Promote proliferation and invasion of NPC cells	Zheng et al. (2019)
Leukemia	Clinical Samples; cells; mice	Oncogene	METTL3; METTL14; WTAP; YTHDF1; FTO; IGF2BP1	Promote AML cells proliferation and leukemia cells self-renewal, growth and metabolism	(Bansal et al., 2014; Vu et al., 2017; Li et al., 2018a; Weng et al., 2018)
Gastroinestinal tumor
Hepatocellular carcinoma	Clinical Samples; cells; mice	Oncogene	METTL3; METTL14; YTHDF1; KIAA1429; WTAP; YTHDF2	Induce HCC cells proliferation, migration, invasion and metastasis	(Chen et al., 2018; Cheng et al., 2019; Müller et al., 2019)
	Cells; mice	Suppressor	METTL14	Suppress tumor invasion and metastasis	Ma et al. (2017)
Gastric carcinoma	Cells, Clinical samples	Oncogene	METTL3; ALKBH5	Promote proliferation, tumor angiogenesis, invasion and metastasis of GC	(Zhang et al., 2019a; Wang et al., 2020e)
Colorectal cancer	Cells, Clinical samples, mice	Oncogene	METTL3; FTO; WTAP; YTHDC2; YTHDF1; IGF2BPs	Promote the proliferation, migration, invasion and EMT of CRC cells	(Tanabe et al., 2016; Zhang et al., 2016; Shen et al., 2018; Wu et al., 2019b; Li et al., 2019c)
	Cells, clinical samples	Suppressor	METTL3; METTL14	Suppress CRC proliferation and migration	(Deng et al., 2019; Chen et al., 2020b)
Pancreatic cancer	Cells, clinical samples	Oncogene	METTL3; YTHDF2	Promote cell proliferation, migration, and invasion	(Chen et al., 2017; Zhang et al., 2019b)
	Cells, clinical samples	Suppressor	ALKBH5; YTHDF2	Suppress cancer migration, invasion, and EMT	(Chen et al., 2017; He et al., 2018)
Urological cancers
Bladder cancer	Cells, clinical samples, mice	Oncogene	METTL3; FTO; ALKBH5	Promote BC cells proliferation, colony formation, invasion and metastasis; inhibit cell apoptosis	(Cai et al., 2018; Wang et al., 2020f)
	Clinical samples	Suppressor	METTL14	Inhibit bladder TIC self-renewal and tumorigenesis	Gu et al. (2019)
Renal cell cancer	Cells, clinical samples, mice	Oncogene	WTAP	Enhance cell proliferation abilities	Tang et al. (2018b)
	Cells, clinical samples, mice	Suppressor	METTL3; FTO	Suppress tumor growth, proliferation, migration, invasion function and cell cycle of RCC and induce apoptosis	(Li et al., 2017d; Zhuang et al., 2019)
Prostate cancer	Cells	Oncogene	METTL3; YTHDF2	Promote tumor cells proliferation, survival, colony formation, and migration	Cai et al. (2019)
Reproductive neoplasms
Breast cancer	Cells, clinical samples, mice	Oncogene	METTL3; FTO; ALKBH5	Promote BC cells proliferation, colony formation and metastasis; inhibit the apoptosis	(Niu et al., 2019; Wang et al., 2020f)
Ovarian cancer	Cells, clinical samples, mice	Oncogene	METTL3; ALKBH5; IGF2BP1	Promote the proliferation and invasion in vitro and in vivo	(Hua et al., 2018; Müller et al., 2019)
Cervical carcinom	Cells, clinical samples	Oncogene	FTO	Promote cell proliferation and migration; induce resistance	Zou et al. (2019)
Endometrial cancer	Cells, clinical samples, mice	Suppressor	METTL3/METTL14	Inhibit the proliferation and tumorigenicity	Liu et al. (2018b)
Skin tumors
Melanoma	Cells, clinical samples, mice	Oncogene	FTO	Increase tumor growth	Yang et al. (2019a)
	Cells, clinical samples, mice	Suppressor	YTHDF1	Restrain cell growth and migratory ability	Jia et al. (2019)
Squamous cell carcinoma	Cells, clinical samples, mice	Oncogene	METTL3	Promote tumorigenicity	Zhou et al. (2019)
Neurodegenerative diseases:
Alzheimer’s disease	Mice, clinical samples	Up- regulation	METTL3; IGF2BP2; RBM15B	—	(Han et al., 2020; Deng et al., 2021)
	Cells, mice, clinical samples	Down- regulation	METTL3; FTO	—	(Huang et al., 2020b; Han et al., 2020), (Zhao et al., 2021)
Parkinson’s disease	Cells	Down- regulation	HNRNPC	—	Quan et al. (2021)
Cardiovascular disease:
Hypertension	Rat	—	—	The m6A methylation level reduce	Wu et al. (2019a)
Cardiac hypertrophy	Cells, mice	Up- regulation	METTL3; FTO	Promote cardiomyocyte hypertrophy both in vitro and in vivo	(Gan et al., 2013; Dorn et al., 2019), (Berulava et al., 2020)
Heart failure	Clinical samples and mice	Up- regulation	METTL3, METTL4, KIAA1429, FTO, YTHDF2	Data from MeRIP-seq	Zhang et al. (2021)
	Clinical sample, preclinical pig, mice, cells	Down- regulation	FTO	Increase m6A in RNA and decrease cardiomyocyte contractile function	Mathiyalagan et al. (2019)
Atherosclerosis	Cells, mice, clinical sample	Up- regulation	METTL3, METTL14, IGF2BP1	Promote cardiovascular endothelial cell proliferation and invasion; aggravates endothelial inflammation, angiogenesis and atherosclerosis	(Zhang et al., 2020b; Jian et al., 2020; Dong et al., 2021)
Diabete mellitus	Clinical sample, cells	Up- regulation	FTO, METTL3	Induce mRNA expression of FOXO1, G6PC, and DGAT2	(Yang et al., 2019b; Yang et al., 2020b)
	Cells, mice, clinical sample	Down- regulation	METTL3, METTL14	regulated functional maturation and mass expansion of neonatal β-cells	(De Jesus et al., 2019; Liu et al., 2019; Men et al., 2019; Wang et al., 2020d)