Table 1.

Multiple functions exerted by RNA m6A methylation in various breast cancer cell lines

Types	Component	Regulation	Sources	Subtypes	Related targets	Key biological function	Ref.
Writers	MELLT3	Up-regulation	MCF-7 MDA-MB-231 MDA-MB-453 MDA-MB-468 MCF-10A	Luminal A Basal Her2+ Basal Basal	let-7 g, Bcl-2	1.METTL3 accelerate cell proliferation and migration. 2.Knockdown METTL3 reduce proliferation and accelerate cell apoptosis.	[22, 23]
		Down	MDA-MB-231 MDA-MB-468	Basal Basal	COL3A1	METTL3 overexpression suppress migration, invasion, and adhesion.	[24]
	RBM15	Uncertain	MCF-7, T47D	Luminal A	BAP1	RBM15 mediate cell growth and invasion.	[25]
	WTAP	Down	MCF-7 MDA-MB-231	Luminal A Basal	KGF, Erk1, Erk2	1.WTAP mediate proliferation and motility of breast cancer cells. 2.Prompt cell motility and invasion.	[26, 27]
	METTL14	Up-regulation	BT549 T47D, MCF-7 SKBR3 MDA-MB-231 MDA-MB-436	Basal Luminal A Her2+ Basal Basal	CXCR4, CYP1B1, Hsa-miR-146a-5p	1.LNC942 prompt cell proliferation and growth by targeting METTL14. 2.METTL14 effect hsa-miR-146a-5p expression and promote the migration and invasion, little effect on cell proliferation.	[28–30]
		Down	MDA-MB-231	Basal	–	Over expression of METTL14 remarkably suppressed cell growth and migration.	[26]
	KIAA1429	Up-regulation	MCF-7 SUM1315 MDA-MB-231	Luminal A Basal Basal	CDK1	KIAA1429 prompt proliferation, colony formation, migration, invasion, and metastasis.	[31, 32]
		Down	Breast cancer	Her2+	–	–	[26]
	CBLL1	Up-regulation	MCF-7 Hakai cells	Luminal A Luminal	ERα	CBLL1 inhibit cell proliferation and migration.	[33–35]
Erasers	FTO	Up-regulation	4 T1 MCF-7 SKBR-3 MDA-MB-231 MDA-MB-453	Basal Luminal A Her2+ Basal Her2+	BNIP, FTO/miR-181b-3p/ARL5B pathway	1.Promotes tumor growth and metastasis by inhibiting BNIP3. 2.Promote cell invasion and migration in vitro. 3.Promotes development and aggressiveness of breast cancer.	[36–40]
	ALKBH5	Up-regulation	MCF-7, T47D SUM-159 MDA-MB-231 MDA-MB-435	Luminal A Basal Basal HER2+	NANOG	1.HIF1α and HIF2α prompt ALKBH5expession. 2.ALKBH5 is required for breast cancer tumorigenicity and lung metastasis. 3.ALKBH5 knockdown to increased proliferation and migration.	[26, 30]
Readers	FMR1	Up-regulation	4 T1	Basal	E-cadherin, Vimentin	1.FMR1 prompt tumor growth, metastasis and cell invasion. 2.CHIP up regulates FMR1 expression.	[41–43]
	FXR1	Up-regulation	BT549 MCF-7 MDA-MB-231	Basal Luminal A Basal	ECT2, PRKCI, Myc	1.FXR1 prompt cell invasion.	[44–46]
	IGF2BP1	Up-regulation	T47D MDA-MB-231MDA-MB-157	Luminal A Basal Basal	IGF2, ACTB, MYC, CD44, CTNNB, BTRC, β-catenin	IGF2BP1 inhibit cell proliferation, tumor growth and pulmonary metastatic tumor.	[47–52]
	IGF2BP2	Up-regulation	SKBR3 MCF-7 MDA-MB-231MDA-MB-435MDA-MB-468 LM2-4 cells	Her2+ Luminal A Basal Basal Basal Basal	CTGF, IGF-2, IGF-1, ERK, PI3K/Akt pathways	1.IGF2BP2 prompt cell migration and reduced cell adhesion by targeting CTGF mRNA. 2.IGF2BP2 stimulate cell proliferation, growth and differentiation. 3.miR-1193 also suppressed IGF2BP2 translation. 4.IGFBP2 mediate endothelial recruitment through IGF1/IGF1R pathways.	[53–56]
	IGF2BP2/IGF2BP3	Up-regulation	MDA-MB-157 MDA-MB-231 MCF-7, T47D BT474	Basal Basal Luminal A Luminal B	microRNA-200a, CNOT1	IGF2BP2/IGF2BP3 cooperate increase cell migration and invasion by targeting microRNA-200a.	[57]
	IGF2BP3	Up-regulation	T47D, MCF-7 HCC1937 SUM-1315 MDA-MB-231MDA-MB-435 MDA-MB-468 SKBR3	Luminal A Basal Basal Basal Basal Basal Her2+	EMT, ABCG, EGFR signaling, CD44/CD44 + Fbs/IGF2	1.IGF2BP3 increase cell migration and invasion. 2.IGF2BP3 prompt EMT and Blockade of miR-3614 maturation.	[25, 57–67]
	HNRNPC	Up-regulation	T47D MCF-7 MDA-MB-435	Luminal A Luminal A Basal	IRF3/7, ISGF3, IFNβ	1.HNRNPC prompt cell proliferation, migration, invasion and metastasis. 2.Repression of HNRNPC arrested the proliferation and tumorigenesis.	[68–70]
	HNRNPA2B1	Up-regulation	MCF-7 MCF-10A MDA-MB-231 LCC9	Luminal A Basal Basal Luminal	STAT3, ERK1, ERK2	1.HNRNPA2B1 prompt in cancer development, progression, gene expression. 2.HNRNPA2B1 associate with endocrine resistance. 3.Knockdown of HNRNPA2B1 inhibit proliferation.	[71, 72]
		Down	MDA-MB-231 MCF-7 cells	Basal Luminal A	PFN2, Wnt pathway, ERK/MAPK/Twist pathway	HNRNPA2B1 inhibits the growth of xenograft tumours but promotes spontaneous lung metastasis.	[73]
	YTHDF1 YTHDF2	Up-regulation	MCF-7 MDA-MB-231 MDA-MB-468	Luminal A Basal Basal	–	1.YTHDF1/2 regulate the expression of YTHDF3. 2.YTHDF1/2 enhance cell proliferation, migration and invasion.	[17, 31, 36, 74–76]
	YTHDF3	Up-regulation	MDA-MB-231 HCC1954 4 T1	Basal Her2+ Basal	ST6GALNAC5, GJA1, EGFR	1.YTHDF3 promotes brain endothelial adhesion, extravasation, invasion, angiogenesis, and cell-astrocyte interaction. 2.Knockdown of YTHDF3 significantly decrease brain metastasis in mouse models. 3.miR-106b-5p down regulate the expression of YTHDF3.	[68, 77]
	eIF3A	Uncertain	MCF-7 ZR-75-1 MDA-MB-231 MDA-MB-453MDA-MB-468	Luminal A Luminal B Basal Her2+ Basal	4EBP1, M2 protein	eIF3A facilitate the proliferation or migration.	[78–81]
	G3BP1	Up-regulation	MCF-7 SKBR3 MDA-MB-231 MDA-MB-468 BT549	Luminal A Her2+ Basal Basal Basal	PMP22, EMT, ZEB1, TGF-b signaling	1.G3BP1 facilitate tumor invasion and migration. 2.G3BP1 involve in vesicle trafficking.	[82–86]