Novel insights into the m6A-RNA methyltransferase METTL3 in cancer

Cai, Yiqing; Feng, Rui; Lu, Tiange; Chen, Xiaomin; Zhou, Xiangxiang; Wang, Xin

doi:10.1186/s40364-021-00278-9

Biomarker Research

Table 1 Multiple functions of METTL3 in human cancer

From: Novel insights into the m⁶A-RNA methyltransferase METTL3 in 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]
		Suppressor	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]
PC	Up	Oncogene	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]
OSCC	Up	Oncogene	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]
			AFF4	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]
GBM	Up	Oncogene	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]
CC	Up	Oncogene	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]
AML	Up	Oncogene	PTEN	Suppresses cell differentiation by inhibiting the AKT pathway	[119]
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]

Back to article page

ISSN: 2050-7771

Contact us

General enquiries: journalsubmissions@springernature.com