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Table 1 Multiple functions exerted by RNA m6A methylation in various breast cancer cell lines

From: The emerging role of RNA N6-methyladenosine methylation in breast cancer

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.

[28,29,30]

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.

[33,34,35]

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.

[36,37,38,39,40]

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.

[41,42,43]

FXR1

Up-regulation

BT549

MCF-7

MDA-MB-231

Basal

Luminal A

Basal

ECT2, PRKCI,

Myc

1.FXR1 prompt cell invasion.

[44,45,46]

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.

[47,48,49,50,51,52]

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.

[53,54,55,56]

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, 57,58,59,60,61,62,63,64,65,66,67]

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.

[68,69,70]

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, 74,75,76]

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.

[78,79,80,81]

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.

[82,83,84,85,86]