Table 1.

Opposite Roles of m6A regulators in Tumorigenesis

m6A regulator	Tumor type	Role	Key results	Ref
METTL3	Colorectal cancer	−	(1) Positive expression of METTL3 was significantly associated with longer survival time (2) METTL3 suppresses colorectal cancer proliferation and migration through p38/ERK pathways	[62]
		+	(1) METTL3 facilitates tumor progression via an m6A-IGF2BP2-dependent mechanism in colorectal carcinoma (2) METTL3 promotes CRC cell stemness by increasing the expression of SOX2	[63]
		+	METTL3 promotes metastasis of colorectal cancer via miR-1246/SPRED2/MAPK signaling pathway	[64]
	Renal clear cell carcinoma	+	(1) METTL3 might be involved in the promotion proliferation through PI3K-AKT-mTOR pathway (2) METTL3 increased cell cycle arrest in G1 phase by promoting a gain in P21 expression	[65]
		−	METTL3 inhibites cellular migration and invasion through EMT pathway	[65]
	Breast cancer	+	Hepatitis B X-interacting protein(HBXIP)-elevated METTL3 promotes the progression of breast cancer via inhibiting tumor suppressor let-7 g	[66]
		+	METTL3 promotes the breast cancer progression via targeting Bcl-2	[67]
		−	Reduced expression of METTL3 predicts poor prognosis in breast cancer	[68]
YTHDF2	Hepatocellular carcinoma	+	miR145 modulates m6A levels by targeting the 3’-UTR of YTHDF2 mRNA and is able to suppresses proliferation of hepatocellular carcinoma	[69]
		+	YTHDF2 facilitates METTL3-mediated SOCS2 m6A modification and degradation thereby reducing the tumor suppressive effect of SOCS2	[70]
		−	(1) Overexpression of YTHDF2 suppresses hepatocellular carcinoma cell proliferation and growth in vitro and in vivo (2) YTHDF2 inhibits ERK/MAPK signaling cascades by destabilizing the EGFR mRNA in hepatocellular carcinoma cells	[71]
	Pancreatic cancer	+	(1) YTHDF2 orchestrates EMT and proliferation in pancreatic cancer cells (2) YTHDF2 promotes tumor proliferation by activating AKT/GSK3β/cyclin D1	[15]
		−	YTHDF2 suppresses metastasis by destabilizing YAP mRNA	[15]

+: promoting effect; −: suppressing effect