Table 1.

The role of different m6A regulators in esophageal carcinoma

m6A regulators	Genes	Location	Role	Mechanism	Function
Writer
METTL3	–	–	Oncogene	Activating the Wnt3/β-catenin and AKT signaling pathways	Promoting ESCC cell proliferation
	APC	mRNA	Tumor suppressor	Reducing APC expression	Promoting ESCC cell proliferation and tumour development
	GLS2	mRNA	Oncogene	GLS2 as a downstream Target of METTL3	Promoting ESCC cell migration and invasion
	SNHG3 and miR-186-5p	mRNA and micro-RNA	–	SNHG3/miR-186-5p induced by platinum, was involved in regulating m6A level by targeting METTL3	Regulating m6A level might be a novel way to enhance the platinum efficacy
	IFIT2	mRNA	Tumor suppressor	IFIT2 mRNA and protein expression were both downregulated by METTL3 overexpression	IFIT2 overexpression Inhibiting ESCC cell proliferation and invasion
	TNFR1	mRNA	Oncogene	TNFR1 regulates the activation of MAPK and NF-κB signaling pathways	The METTL3-m6A-TNFR1-ATXN2 axis plays oncogenic roles in ESCC through MAPK and NF-κB signaling pathways
	miR-320b	Micro-RNA	Oncogene	METTL3 could interact with DGCR8 protein and positively modulate pri-miR-320b maturation process in an N6-methyladenosine (m6A)-dependent manner	miR-320b promotes the proliferation, migration, invasion, and epithelial-mesenchymal transition progression of ESCC cells
	miR-20a-5p	Micro-RNA	Oncogene	METTL3 promote m6A modification and the binding of DGCR8 to miR-20a-5p to further elevate the miR-20a-5p expression and inhibit NFIC transcription	miR-20a-5p upregulation facilitates ESCA cell invasiveness and migration by targeting Nuclear Factor I-C(NFIC) transcription
	NOTCH1	mRNA	Oncogene	NOTCH1 signaling pathway is an important downstream target of METTL3 and is essential for its function in promoting ESCC progression	METTL3-catalyzes m6A modification promotes NOTCH1 expression and the activation of the Notch signaling pathway
	EGR1	mRNA	Oncogene	METTL3 increases m6A in EGR1 mRNA and enhances its stability in a YTHDF3-dependent manner	METTL3 promotes cancer metastasis by activating EGR1/Snail signaling in an m6A-dependent manner
	COL12A1	mRNA	Oncogene	COL12A1 serves as a potential target gene of METTL3 and acts as an oncogene in the progression of ESCC	METTL3 enhanced proliferation and metastasis of ESCC through COL12A1/MAPK signaling pathway
METTL14	miR-99a-5p	micro-RNA	Tumor suppressor	METTL14 upregulates miR-99a-5p by modulating m6A-mediated, DiGeorge critical region 8-dependent pri-mir-99a processing	METTL14/miR-99a-5p/TRIB2 axis shows that it is positively associated with cancer stem-like cells characteristics and radioresistance of ESCC
Eraser
FTO	MMP13	mRNA	Oncogene	Stabilizing MMP13 mRNA	Enhancing ESCC cell viability and migration
	HSD17B11	mRNA	Oncogene	FTO promote the formation of lipid droplets in EC cells by enhancing HSD17B11 expression	High expression level of HSD17B11 promoting the aggregation of lipid droplets
	ERBB2	mRNA	Oncogene	ERBB2 is the target gene of FTO in ESCC cells	YTHDF1 stabilizes ERBB2 mRNA via decoding the m6A modification and ERBB2 involves in the tumorigenesis of ESCC progression
	LINC00022	IncRNA	Oncogene	FTO in ESCC decreased m6A methylation of LINC00022 transcript, leading to the inhibition of LINC00022 decay via the m6A reader YTHDF2	LINC00022 directly binds to p21 protein and promotes its ubiquitination-mediated degradation, thereby facilitating cell-cycle progression and proliferation
ALKBH5	CDKN1A	mRNA	Tumor suppressor	Stabilizing CDKN1A mRNA	Promoting ESCC cell proliferation
	miR-193-3p	micro-RNA	Oncogene	inhibiting miR-193a-3p expression	Promoting the proliferation, migration and invasion ability of ESCC cells
	miR-194-2	micro-RNA	Oncogene	ALKBH5 regulates RAl1 by reducing miR-194-2-mediated RAl1 suppression	ALKBH5 suppresses esophageal cancer malignancy by inhibiting m6A/DGCR8-dependent miRNA biogenesis and unleashing RAl1 expression
Reader
WTAP	CPSF4	mRNA	Tumor suppressor	WTAP mediated m6A of CPSF4 mRNA in an YTHDF2-dependent manner	Decreasing CPSF4 expression in an m6A-dependent manner facilitates ESCC tumour growth and metastasis
IGF2BP2	LNC-CCAT2	IncRNA	Oncogene	Inhibiting miR-200b to upregulate the IGF2BP2/TK1 Axis	Ensuing promotion of the development of ESCC
IGF2BP2 and IGF2BP3	LINC01305	IncRNA	Oncogene	linc01305 promotes HTR3A mRNA stability through interacting with IGF2BP2 and IGF2BP3	HTR3A promoting migration and proliferation of ESCC
YTHDF1-3	APC	mRNA	Tumor suppressor	Mediating APC mRNA degradation	Promoting β-catenin-mediated downstream gene expression, aerobic glycolysis and ESCC cell proliferation
YTHDF1	LINC00278	IncRNA	Tumor suppressor	Promoting the translation efficiency of YY1BM	Promoting apoptosis of ESCC cell
	HLA complex P5 (HCP5) and HK2	Endogenous retroviral gene	Oncogene	Promoting the Warburg effect (aerobic glycolysis) of ESCC cells	The turbulence of HCP5/YTHDF1/HK2 axis may be responsible for ESCC carcinogenicity
YTHDC2	rs2416282	SNP	Tumor suppressor	Increasing YTHDC2 expression by allele-specific binding to transcription factors	rs2416282 reducing ESCC risk in Chinese population by altering the expression of YTHDC2
HNRNPA2B1	ACLY and ACC1	Enzymes	–	Up-regulating the fatty acid synthesis enzymes ACLY and ACC1	Promoting ESCC progression via up-regulation of fatty acid synthesis enzymes ACLY and ACC1 and cellular lipid accumulation
	miR-17-92 cluster	Micro-RNA	ONCOGENE	Correlating with the cell cycle and RNA transport signaling pathways	HNRNPA2B1 affects tumor-promoting signaling pathways by regulating the expression of the miR-17-92 cluster
HNRNPL	CASC8	lncRNAs	Oncogene	CASC8 interacte with heterogeneous nuclear ribonucleoprotein L (hnRNPL) and inhibited its polyubiquitination and proteasomal degradation, thus stabilizing hnRNPL protein levels and activating the Bcl2/caspase3 pathway	CASC8 decreases the cisplatin sensitivity of ESCC cells and promoted ESCC tumor growth