The role of m6A, m5C and Ψ RNA modifications in cancer: Novel therapeutic opportunities

Nombela, Paz; Miguel-López, Borja; Blanco, Sandra

doi:10.1186/s12943-020-01263-w

Molecular Cancer

Table 1 Alterations in N6-methyladenosine writers, erasers and readers in cancer. AML: Acute myeloid leukaemia; HCC: Hepatocellular Carcinoma; GSC: Glioma Stem Cells; LncRNA: long non-coding RNA

From: The role of m⁶A, m⁵C and Ψ RNA modifications in cancer: Novel therapeutic opportunities

Factor/Enzyme	Cancer type	Alteration	Mechanism	Ref
Writers
METTL3	AML	Upregulated	METTL3 promotes translation of oncogenes’ mRNAs, inhibiting cell differentiation and apoptosis.	[117, 118]
	Bladder Cancer	Upregulated	METTL3 accelerates miR221/222 maturation.	[104, 157, 321, 322]
	Breast Cancer	Upregulated	METTL3 inhibits miRNA let-7 and induces proliferation and survival.	[119]
	Colon Cancer	Upregulated	METTL3 increases miRNA-1246 expression inducing metastasis.	[120]
	Endometrial Cancer	Downregulated	METTL3 regulates the expression of members of AKT pathway and inhibits cell proliferation.	[111]
	Glioblastoma	Downregulated	METTL3 decreases oncogene expression and inhibits the self-renewal.	[35, 136]
	Glioblastoma/ Gastric Cancer	Upregulated	METTL3 increases the stability of oncogenic mRNAs.	[123, 323]
	HCC	Upregulated	METTL3 inhibits mRNA expression of tumour suppressors, increasing proliferation and metastasis.	[56, 114]
	Lung/Colon Cancer	Upregulated	METTL3 promotes oncogenes’ mRNA translation.	[113]
	Lung Cancer	Upregulated	METTL3 increases miR-143-3p expression and induces oncogenes translation.	[43, 324, 325]
	Melanoma	Upregulated	Unknown.	[326, 327]
	Osteosarcoma	Upregulated	METTL3 increases mRNA expression of oncogenes.	[328]
	Ovarian Cancer	Upregulated	METTL3 stimulates the translation of oncogenes.	[329, 330]
	Prostate Cancer	Upregulated	METTL3 increases oncogene mRNA expression.	[121]
	Prostate Cancer	Upregulated	METTL3 increases the mRNA stability of cell adhesion genes.	[122]
	Renal Cell Carcinoma	Upregulated	Unknown.	[124, 331, 332]
METTL14	AML	Upregulated	METTL14 increases oncogenes’ mRNA stability and translation.	[40]
	Bladder Cancer	Downregulated	METTL14 increases oncogenes’ mRNA decay.	[333]
	Colon Cancer	Downregulated	METTL14 regulating primary miRNA processing of YAP an SP1 pathways or downregulating lncRNA XIST.	[334, 335]
	Endometrial Cancer	Downregulated	METTL14 regulates the expression of members of AKT pathway and inhibits cell proliferation.	[111]
	HCC	Downregulated	METTL14 induces an increase of pri-miR-126 expression that suppresses tumour metastases.	[12]
	Renal Cell Carcinoma	Downregulated	METTL14 represses the translation of P2RX6 increasing invasion.	[336]
	Pancreatic Cancer	Downregulated	Unknown.	[337]
Erasers
FTO	AML	Upregulated	FTO enhances oncogenes’ mRNA stability.	[36, 37]
	Bladder Cancer	Downregulated	Unknown.	[338]
	Breast Cancer	Upregulated	FTO downregulates the expression of tumour suppressor genes.	[134]
	Cervical Cancer	Upregulated	FTO promotes translation of oncogenes, promoting migration and drug resistance.	[131, 132]
	Glioblastoma	No change	FTO regulates of oncogene expression.	[35, 136]
	HCC	Downregulated	Unknown.	[339]
	Lung Cancer	Upregulated	FTO regulates MZF1 expression.	[133]
	Melanoma	Upregulated	FTO increases stability of critical immunotherapy resistance and pro-tumorigenic melanoma cell-intrinsic genes.	[38, 130]
	Pancreatic Cancer	Upregulated	FTO promotes oncogene mRNA stability.	[340]
ALKBH5	AML	Upregulated	Unknown.	[341, 342]
	Breast Cancer	Upregulated	ALKBH5 enhances mRNA stability of stem cell self-renewal genes.	[135, 137]
	Glioblastoma	Upregulated	ALKBH5 sustains oncogene expression.	[136]
	Gastric Cancer	No change	Binding to NEAT1 lncRNA, which promotes invasion and metastasis.	[138]
	Lung Cancer	Downregulated	ALKBH5 reduces oncogene expression and inhibits oncogenic miRNA.	[343]
	Osteosarcoma	Upregulated	ALKBH5 decreases the decay of the lncRNA PVT1.	[344]
	Ovarian Cancer	Upregulated	ALKBH5 enhances stability of oncogenes, self-renewal genes and survival genes.	[139, 142]
	Pancreatic Cancer	Upregulated	Unknown.	[140, 141]
Readers
YTHDC2	Colon Cancer	Upregulated	YTHDC2 upregulates expression of pro-metastatic genes.	[143]
YTHDF1	Colon Cancer	Upregulated	Induces Wnt-β-catenin pathway and unknown.	[144, 345]
	Melanoma	Downregulated	YTHDF1 promotes the translation of tumour suppressor genes.	[146]
	Ovarian Cancer	Upregulated	YTHDF1 increases translation of oncogenes.	[145]
YTHDF2	AML	Upregulated	YTHDF2 reduces the stability of transcripts such as TNFRSF2.	[147]
	HCC	Upregulated	YTHDF2 inhibits SOCS2 mRNA expression.	[56]
	HCC	Downregulated	YTHDF2 promotes the degradation of EGFR mRNA.	[149]
	Lung Cancer	Upregulated	YTHDF2 promotes the translation of 6PGD mRNA.	[148]

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ISSN: 1476-4598

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