Table 1.

Multiple functions of METTL3 in human cancer

Cancer type	Expression	Role	Targets	Biological functions and underlying mechanisms	Refs
GC	Up	Oncogene	MYC	Promotes tumor progression by enhancing MYC expression	[44, 45]
			SEC62	Promotes anti-apoptosis by depressing the apoptosis pathway	[46]
			HDGF	Actives aerobic glycolysis by GLUT4 and ENO2 to promote tumor growth	[48]
			LncRNA LINC00470	Potentiates tumor growth by functional inhibition of PTEN	[40]
			ZMYM1	Promotes EMT by inhibiting E-cadherin expression	[49]
			GIF-1 and α-SMA	Enhances cell mobility and instant metastasis	[43]
			ARHGAP5	Enhances chemoradioresistance by stabilizing ARHGAP5 mRNA	[41]
		Suppressor	BATF2	Suppresses tumor progress by inhibiting the ERK pathway	[50]
			DGCR8	Enhances chemosensitivity to mTOR inhibitor	[51]
HCC	Up	Oncogene	SOCS2	Enhances cell proliferation, migration and stemness maintenance	[54]
			RDM1	Activates the Ras/Raf/ERK pathway to promote tumor progress	[55]
			Snail	Preserves oncogenic properties by up-regulating Snail	[56]
			miR-6079 and LINC00958	Enhances aerobic glycolysis by activating the mTOR pathway	[57, 58]
		Suppressor	FOXO3	Promotes sorafenib sensitivity, inhibits angiogenesis and autophagy	[59]
Gallbladder cancer	Up	Oncogene	miR-92b-3p	Inhibits PTEN to promote tumor progression	[60]
CRC	Up	Oncogene	SOX2	Promotes self-renewal, cell growth and metastasis	[61]
			Cyclin E1	Enhances tumor growth	[62]
			miR-1246	Promotes tumor progression by activating the MAPK pathway	[35]
			SOCS2 and YPEL5	Promotes tumor progression	[31, 63]
			HK2 and GLUT1	Accelerates aerobic glycolysis to promote tumor growth	[64]
			P53 and LGR5	Induces chemotherapeutic resistance	[66, 67]
			STAT1 and IRF1	Enhances resistance to anti-PD-1 treatment by inhibiting the IFN pathway	[68]
PC	Up	Oncogene	miR-25-3p	Promotes tumor growth and metastasis by activating the PI3K/AKT pathway	[70]
			MAPK	Induces chemo- and radio-resistance	[71]
NPC	Up	Oncogene	ZNF750	Suppresses cell apoptosis by inhibiting the ZNF750-FGF14 pathway	[75]
			EZH2	Enhances metastasis by up-regulating CDKN1C	[74]
			Snail	Enhances metastasis by increasing the translation of Snail mRNA	[77]
OSCC	Up	Oncogene	BMI1	Promotes cell proliferation and metastasis	[78]
			MYC	Promotes tumor progression by increasing the expression of MYC	[79]
NSCLC	Up	Oncogene	YAP	Stimulates stem cell generation and promotes tumor progression	[36]
			lncRNA ABHD11-AS1	Enhances aerobic glycolysis to promote tumor progression	[80]
			PI3K	Accelerates tumor growth by activating the AKT pathway	[38]
			EZH2	Enhances tumor metastasis by inhibiting the expression of EZH2	[80]
			miR-143-3p and VASH1	Enhances brain metastasis by eliminating miR-143-3p and VASH1	[81]
			autophagy	Induces chemotherapeutic resistance	[82]
BC	Up	Oncogene	CDCP1	Stimulates cell proliferation and transformation by enhancing CDCP1 expression	[88]
			ITGA6	Enhances aggressive features of tumor cell by enhancing ITGA6 expression	[89]
			AFF4	Accelerates tumor growth and invasion by activating MYC	[90]
				Maintains self-renewal capability of stem cells by activating SOX2	[91]
			SETD7 and KLF4	Promotes tumor progression by inhibiting the expression of SETD7 and KLF4	[92]
			pri-miR221/222	Induces poor prognosis of BC by functional inhibition of PTEN	[34]
PCa	Up	Oncogene	MYC	Promotes tumor progression	[94]
			LEF1	Promotes cell proliferation and metastasis by activating the Wnt pathway	[95]
			GLI1	Enhances cell growth and survival by activating the SHH pathway	[96]
			HuR	Promotes bone metastasis by enhancing the expression of ITGB1	[97]
GBM	Up	Oncogene	SOX2, SALL2, OLIG2 and POU3F2	Elevates the translation of oncogenes to activate stem-like cell	[99]
			SOX2	Enhances γ-irradiation resistance by elevating SOX2 expression	[100]
Breast cancer	Up	Oncogene	BCL-2, HBXIP and p21	Promotes cell proliferation by enhancing the expression of oncogenes	[37, 103, 104]
			Pri-miRNA-221-3p	Induces adriamycin resistance by facilitating miRNA maturation	[105]
			AK4	Induces tamoxifen resistance	[106]
TNBC	Up	Suppressor	COL3A1	Inhibits cell mobility and ECM adhesion	[107]
Ovarian cancer	Up	Oncogene	eIF3c, CSF-1 and FZD10	Promotes tumor progression and poor prognosis	[108]
			AXL	Promotes tumor progression by increasing the translation of AXL	[109]
			BCL-2	Suppresses cell apoptosis by inhibiting BCL-2 related pathway	[110]
			miR-126-5p	Enhances cell growth, migration and invasion by inhibiting PTEN	[111]
Endometrial cancer	Up	Suppressor	AKT regulators	Inhibits proliferation and tumorigenicity by inhibiting the AKT pathway	[112]
CC	Up	Oncogene	RAB2B	Enhances cell proliferation by increasing RAB2B expression	[115]
			PDK4 and HK2	Enhances aerobic glycolysis to promote tumor growth and chemoresistance	[116]
AML	Up	Oncogene	MYC and BCL-2	Promotes cell growth and anti-apoptosis	[119]
			PTEN	Suppresses cell differentiation by inhibiting the AKT pathway
DLBCL	Up	Oncogene	PEDF	Promotes cell proliferation by activating the Wnt pathway	[123]
HNSCC	Up	Oncogene	lncRNA LNCAROD	Promotes cell proliferation and metastasis	[124]
TC	Up	Oncogene	HNF1A	Enhances migration by activating the Wnt pathway	[125]