Table 2.

Roles of m5C enzymes in cancer

Cancer type	Enzyme and relative RNA	Aberrant expression	Target	Effect of targets	Roles in cancer	Refs.
HCC	NSUN2	Upregulation	FZR1 mRNA	Enhances stability	Enhances the growth of HCC cells and tumors	[58]
			H19 lncRNA	Enhances stability	Promotes proliferation, migration, invasion, and angiogenesis and inhibits apoptosis	[49]
	NOP2	Upregulation	Unknown	–	Promotes carcinogenesis, cell proliferation, and stem cell-like properties	[125]
	NSUN4	Upregulation	Unknown	–	Unknown	[93]
Gastric Cancer	NSUN2	Upregulation	FOXC2 mRNA	Enhances stability	Facilitates proliferation, migration, and invasion	[69]
			p57kip2 mRNA	Represses expression	Promotes the proliferation of GC cells	[39]
GIST	DNMT2	Upregulation	Unknown	–	Unknown	[142]
CRC	circNSUN2	Upregulation	HMGA2 mRNA	Enhances stability	Promotes liver metastasis	[73]
			miR-181a-5p	Repress expression	Enhances ROCK2 expression to promote proliferation and migration and inhibits apoptosis	[46, 70]
	NSUN2	Upregulation	miR-125b	Inhibits processing	Enhances Gab2 expression to promote cell migration	[46]
	NSUN5	Upregulation	Unknown	–	Promotes proliferation and maintains cell cycle	[101]
Glioma	NSUN5	Downregulation	28S rRNA	Deletes m5C3782	Changes ribosome structure, repressing global protein synthesis	[95]
					Activates stress adaptive translational programs	[95]
	NSUN3, DNMT2 and NOP2	Upregulation	Unknown	–	Unknown	[22]
Breast Cancer	NSUN2, NOP2	Upregulation	Unknown	–	Promotes proliferation, migration, invasion, and tumorigenicity of cancer cells	[67, 74]
	NSUN6	Downregulation	MST1 Protein	Inactivation	Activates YAP to promote tumor cell proliferation and bone metastasis	[105]
UCB	NSUN2	Upregulation	HDGF mRNA	Enhances stability	Promotes invasion and metastasis	[10]
Prostate Cancer	DNMT2	Upregulation	Unknown	–	Unknown	[148]
	NOP2	Upregulation	Unknown	–	Promotes metastasis and invasion through the EMT pathway	[18, 19]
ccRCC	NSUN6, NSUN5, NSUN2, NOP2 and DNMT2	Upregulation	Unknown	–	Unknown	[20, 21, 23]
	NSUN3, NSUN4 and NSUN7	Downregulation	Unknown	–	Unknown	[20, 23]
Leukemia	NSUN3, DNMT2	Undetermined	hnRNPK	Enhances integrity	Involved in forming 5-AZA-sensitive active chromatin structure	[81]
	NOP2	Undetermined	RNA-pol-II	Unknown	Involved in forming 5-AZA-resistant active chromatin structure	[81]
Gallbladder Carcinoma	NSUN2	Upregulation	Unknown	–	Promotes growth and tumorigenesis	[149]
LUSC	NSUN3, NSUN4	Upregulation	Unknown	–	Unknown	[79]
Lung adenocarcinoma	NOP2	Upregulation	Unknown	–	Involved in poor differentiation	[26]
CM	NOP2, NSUN5	Upregulation	Unknown	–	Unknown	[24]
	NSUN6, NSUN7	Downregulation	Unknown	–	Unknown	[24]
ESCC	NSUN2	Upregulation	GRB2 mRNA	Enhances stability	Activates PI3K/Akt and ERK/MAPK signaling	[11]
			NMR lncRNA	Unknown	Promotes metastasis and invasion and enhances cisplatin resistance	[50]
HNSCC	NSUN2	Upregulation	Unknown	–	Unknown	[63, 66]
HPSCC	NSUN3	Upregulation	TEAD1 mRNA	Enhances expression	Enhances proliferation and invasion	[71]
PC	NSUN6	Downregulation	CDK10	Enhances expression	Inhibits proliferation	[154]