Table 3 Aberrant mRNA modifications in diseases

m⁶A

AML

FTO

ASB2/ RARA

FTO decreases m⁶A abundance on ASB2 and RARA mRNA in certain subtypes of AML and diminishes the amount of protein

[41, 108]

MYC

FTO decreases m⁶A frequency on MYC mRNA by limiting YTHDF2-mediated RNA decay

[109]

METTL3

BCL2/ PTEN

METTL3 promotes the translation of BCL2 and PTEN mRNA by upregulating m⁶A levels

[110]

SP1

METTL3 supports the expression of SP1 by binding to the unique region with the help of the transcription factor CEBPZ

[111]

METTL 14

MYB/ MYC

METTL14 enhances the expression of MYB and MYC mRNA in AML

[112]

ALKBH5

N.A.

Approximately 10.5% of AML patients carry CNVs of ALKBH5, which predicts poor prognosis and p53 mutations

[113]

Gastric cancer

METTL3

HDGF

METTL3 causes m⁶A to accumulate on HDGF mRNA, which indicates proliferation and poor prognosis of gastric cancer

[114]

ZMYM1

METTL3 enhances the stability of ZMYM1 mRNA to accelerate EMT and metastasis

[115]

SEC62

METTL3 reduces m⁶A on SEC62 with the help with MiR-4429

[116]

Hepatic carcinoma

METTL3

SOCS2

METTL3 works with YTHDF2 together to enhance the degradation of SOCS2 m⁶A-containing mRNA, which leads to HCC

[117]

YTHDF2

EGFR

YTHDF2 suppresses ERK/MAPK signalling cascades and cell proliferation via destabilizing the EGFR mRNA

[118]

METTL14

N.A.

The expression of METTL14 is decreased in HCC, especially in metastatic HCC

[119]

Pancreatic cancer

METTL3

N.A.

METTL3 protein, m⁶A abundance and mRNA levels are much higher in tumour specimens than in para-cancerous specimens

[120]

YTHDF2

YAP

Increased YTHDF2 promotes proliferation and suppresses migration of pancreatic cancer by destabilizing YAP mRNA

[121]

Lung cancer

METTL3

EGFR/ TAZ

METTL3 enhances the translation of EGFR and TAZ mRNA in lung cancer

[56]

SUMOylated METTL3

N.A.

SUMOylated METTL3 promotes NSCLC by diminishing the amount of m⁶A

[122]

YTHDF2

6PGD

YTHDF2 enhances 6PGD mRNA translation by binding to m⁶A sites uniquely in lung cancer cells

[123]

FTO

USP7

FTO stabilizes and increases the expression of USP7 by reducing m⁶A content

[124]

FTO

MZF1

Overexpressed FTO accelerates oncogene MZF1 expression by diminishing m6A and stabilizing MZF1 in LUSC

[125, 126]

Glioblastoma

METTL3/ METTL14

ADAM19

Decreased METTL3 or METTL14 determines the diminution of m⁶A on ADAM19 mRNA, which promotes the expression of protein and contributes to glioblastoma

[127, 128]

ALKBH5

FOXM1

Increased levels of ALKBH5 lead to decreased levels of m⁶A on FOXM1 mRNA and enhance protein translation, which predicts poor prognosis

[129, 130]

METTL3

SOX2

Elevated METTL3 stabilizes SOX2 mRNA and enhances radio-resistance of glioblastoma

[131]

Prostate cancer

YTHDF2

N.A.

Downregulated YTHDF2 suppresses the proliferation and migration of prostate cancer by elevating m⁶A contents

[132]

Bladder cancer

METTL3

PTEN

With the help of pri-miR221/222, upregulated METTL3 leads to downregulated PTEN and tumorigenesis of cancer

[133]

Breast cancer

ALKBH5

KLF4/ NANOG

m⁶A on KLF4 and NANOG can be suppressed by the cooperation of ZNF17 and ALKBH5 to promote protein expression and contribute to breast cancer

[134, 135]

METTL3

HBXIP

Enhanced levels of m⁶A on HBXIP are attributed to increased METTL3 and promote the proliferation of breast cancer stem cells

[136]

FTO

BNIP3

Elevated FTO leads to decreased expression of BNIP3 and metastasis of breast cancer

[137]

Cervical cancer

FTO

β-catenin

High expression of FTO and low levels of β-catenin lead to chemoradiotherapy resistance in cervical squamous cell carcinoma

[138]

Endometrial cancer

METTL14/METTL3

N.A.

Either mutated METTL14 or reduced METTL3 activates the AKT signalling pathway and stimulates proliferation and tumorigenicity by limiting the expression of m⁶A

[139]

Ocular melanoma

YTHDF1

HINT2

YTHDF1 promotes the translation of methylated HINT2 mRNA and inhibits the progression of ocular melanoma

[140]

m¹A

Ovarian/Breast cancer

ALKBH3

CSF-1

Accumulated ALKBH3 indicates improved CSF-1 mRNA expression and invasion of cancer cells

[141]

Gastrointestinal cancer

ALKBH3

ErbB2/ AKT1S1

Aberrant m¹A modifications regulate gastrointestinal cancer by modulating the mTOR pathway associated with cell proliferation

[142]

Urothelial carcinoma

ALKBH3

N.A.

ALKBH3 promotes the progression, angiogenesis and invasion of urothelial carcinomas via NOX-2-ROS and TWEAK/Fn14-VEGF signals

[143]

m⁵C

Skin cancer

NSUN2

N.A.

Inactivating NSUN2 prevents protein translation and stimulates the tumour-initiating population of skin cancer

[144]

Breast cancer

NSUN2

N.A.

NSUN2 is reported to be upregulated at the mRNA and protein levels

[145]

Urothelial carcinoma

YBX1

HDGF

m⁵C modified 3'UTR in HDGF mRNA can be recognized by YBX1 and activate the advancement of UCB

[78]

Lung cancer

N.A.

N.A.

M⁵C RNA modification is upregulated in circulating tumour cells from patients with lung cancer

[146]

Ψ

Prostate cancer

DKC1

N.A.

Certain nucleolar RNAs (H/ACA snoRNAs) and DKC1 that transfer U to Ψ contribute to the progression of cancer

[147]

Haematological malignancies

N.A.

N.A.

H/ACA snoRNAs are limited in acute leukaemia, lymphoma and multiple myeloma

[150,151,152]

I

Hepatocellular carcinoma

ADAR1

AZIN1

Edited AZIN1 stimulates S/G conversion and induces proliferation and poor prognosis in hepatocellular carcinoma

[153, 154]

ADAR1

BLCAP

Increased editing of BLCAP accelerates cell proliferation by activating the Akt/mTOR signalling pathway or STAT3

[158]

Cervical cancer

ADAR1

BLCAP

Increased editing of BLCAP accelerates cell proliferation by activating the Akt/mTOR signalling pathway or STAT3

[157]

Breast cancer

ADAR1

DHFR

Editing of DHFR by ADAR1 stabilizes mRNA and accelerates cell growth

[159]

Gastric cancer

ADAR2

PODXL

Downregulated ADAR2 reduces the decoration on PODXL and increases the malignancy of gastric cancer

[160]

Lung adenocarcinoma

ADARB1

N.A.

ADARB1 has low expression in H358 and A549 lung adenocarcinoma cells

[161]

U

Thyroid carcinoma

UPP1

N.A.

It is reported that the expression of UPP1 significantly depends on lymph node metastasis, tumour stage and size

[164]