Function and clinical significance of N6-methyladenosine in digestive system tumours

Huang, Junchao; Shao, Yingjie; Gu, Wendong

doi:10.1186/s40164-021-00234-1

Experimental Hematology & Oncology

Table 1 The roles of m6A-associated proteins in digestive system tumours

From: Function and clinical significance of N6-methyladenosine in digestive system tumours

Tumour type	m6A Regulators	Role in M6A	Mechanism	Function in cancer	Reference
ESCC	FTO	Eraser	Targets MMP13	Promotes tumour progression	[32]
	METTL3	Reader	Activates Wnt3/β-catenin and AKT signaling pathway	Promotes tumour proliferation and invasion	[33]
	ALKBH5	Eraser	–	Inhibits tumour progression	[36]
	HNRNPC	Reader	–	Promotes tumour progression	[36]
	HNRNPA2B1	Reader	Up-regulates fatty acid synthase ACLY and ACC1	Promotes tumour proliferation, metastasis and invasion	[35]
	YTHDC2	Reader	–	–	[37]
GC	METTL3	Writer	Promotes the m6A modification of GFI1	Promotes tumour cell proliferation and migration	[44]
			METTL3/HDGF/GLUT4/ENO2 pathway	Promotes tumour progression	[46]
			METTL3/ZMYM1/E-cadherin pathway	Promotes tumour progression	[45]
			METTL3/BATF2/p53/ERK pathway	Promotes tumour proliferation and metastasis	[48]
			Promotes the m6A modification of MYC	Promotes tumour progression	[51]
			Regulates several components of MYC gene (such as MCM5, MCM6, etc.)	–	[50]
	METTL14	Writer	PI3K/AKT/mTOR pathway	Inhibits tumour proliferation and invasion	[53]
	YTHDF1	Reader	YTHDF1/FZD7/β-catenin pathway	Promotes tumour progression	[54]
	WTAP	Writer	–	Promotes tumour progression	[60]
	FTO	Eraser	–	Promotes tumour proliferation, metastasis and invasion	[55]
	ALKBH5	Eraser	Decreases methylation of the lncRNA NEAT1	Promotes tumour metastasis and invasion	[143]
CRC	METTL3	Writer	METTL3/IGF2BP2/SOX2 pathway	Promotes tumour progression	[63]
			Stabilizes CCNE1 mRNA	Promotes tumour progression	[64]
			METTL3/miR-1246/SPRED2 /MAPK pathway	Promotes tumour progression	[65]
			Suppresses SOCS2 expression	Promotes tumour progression	[66]
			METTL3/HK2/GLUT1/IGF2BPs pathway	Promotes tumour progression	[67]
			METTL3/GLUT1/mTORC1 pathway	Promotes tumour progression	[144]
			P38 / ERK pathway	Inhibits tumour progression	[62]
			The expression of p53 missense mutation	Acquired multidrug resistance	[69]
	METTL14	Writer	Inhibits the expression of SOX4	Inhibits tumour progression	[70]
			METTL14/miR-375/YAP1 pathway	Inhibits tumour metastasis	[71]
			METTL14/miR-375/SP1 pathway	Inhibits tumour metastasis and invasion	[71]
			METTL14/YTHDF2/lncRNA pathway	Inhibits tumour progression	[72]
	YTHDF1	Reader	Up-regulates the expression of FZD9 and WNT6 and activate Wnt/β-catenin pathway	Promotes tumour progression	[81]
	IGF2BP2	Reader	RNA-protein ternary complex	Promotes tumour progression	[79]
	IGF2BP1	Reader	Upregulates the stability and expression of c-Myc mRNA	Promotes tumour progression	[78]
	FTO	Eraser	Removes the m6A modification of MYC and enhance MYC expression	Promotes tumour proliferation, metastasis and invasion	[76]
HCC	WTAP	Writer	HuR/ETS1/p21/p27 pathway	Promotes tumour progression	[88]
	KIAA1429	Writer	Inhibits ID2 expression	Promotes tumour metastasis and invasion	[89]
			Degrade GATA3 pre-mRNA	Promotes tumour proliferation and metastasis	[90]
			KIAA1429/circ-KIAA1429/ZEB1 pathway	Promotes tumour proliferation, metastasis and invasion	[91]
	YTHDF1	Reader	PI3K/AKT/mTOR pathway	Promotes tumour proliferation	[93]
	YTHDF3	Reader	M6A/YTHDF3/ZEB1 pathway	Promotes tumour proliferation, metastasis and invasion	[91]
	YTHDF2	Reader	Degrades IL11 and SERPINE2 mRNA	Inhibits tumour proliferation	[94]
			Degrades EGFR mRNA	Inhibits tumour progression	[95]
			–	Promotes tumour metastasis	[96]
	METTL14	Writer	Up-regulates miR-126 expression	Inhibits tumour metastasis	[97]
	METTL3	Writer	UBC9/SUMOylated METTL3/Snail pathway	Promotes tumour progression	[106]
			METTL3/miR-873-5p/SMG1 pathway	Promotes tumour progression	[107]
			METTL3/IGF2BP2/FEN1 pathway	Promotes tumour progression	[102]
			METTL3/HBXIP/HIF-1α pathway	Promotes tumour progression	[105]
			METTL3/YTHDF2/SOCS2 pathway	Promotes tumour progression	[100]
			Upregulated LINC00958	Promoted HCC lipogenesis and progression	[112]
	ZCCHC4	Writer	–	Promotes tumour proliferation	[103]
	ALKBH5	Eraser	ALKBH5 / LYPD1 pathway	Inhibits tumour proliferation and invasion	[104]
	FTO	Eraser	–	Inhibits tumour progression	[111]
PDAC	METTL3	Writer	–	Promotes tumour proliferation and invasion	[122]
			METTL3/miR-25-3p/PHLPP2-AKT pathway	Promotes tumour progression	[124]
	METTL14	Writer	Decreases PERP mRNA expression	Promotes tumour proliferation and migration	[123]
	YTHDF2	Reader	–	Promotes tumour proliferation	[125]
	ALKBH5	Eraser	Post-transcriptionally activates PER1	Inhibits tumour proliferation, metastasis and invasion	[126]
			Demethylates lncRNA KCNK15-AS1	Inhibits tumour metastasis	[127]
			Down-regulates the m6A level of WIF-1 and inhibit the activation of Wnt pathway	Inhibits tumour progression	[128]
	FTO	Eraser	Stabilizes bHLH mRNA	Promotes tumour proliferation	[129]
	IGF2BP2	Reader	Up-regulates lncRNA DANCR expression	Promotes tumour proliferation	[130]

ESCC esophageal squamous cell cancer, GC gastric cancer, CRC colorectal cancer, HCC hepatocellular carcinoma, PDAC pancreatic ductal adenocarcinoma

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ISSN: 2162-3619

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