The interplay between m6A RNA methylation and noncoding RNA in cancer

Ma, Shuai; Chen, Chen; Ji, Xiang; Liu, Jinbo; Zhou, Quanbo; Wang, Guixian; Yuan, Weitang; Kan, Quancheng; Sun, Zhenqiang

doi:10.1186/s13045-019-0805-7

Journal of Hematology & Oncology

Table 1 Roles of m6A key members in cancers

From: The interplay between m6A RNA methylation and noncoding RNA in cancer

Proteins	Cancer	Role	Functional classification	mechanism	References
METTL3	Leukemia	Oncogene	Inhibiting differentiation and increasing cell growth in vitro. Inducting differentiation and apoptosis, and put off leukemia in vivo.	Promoting the translation of c-MYC, BCL2, and PTEN	[46]
	Glioblastoma	Tumor suppressor	Suppressing glioblastoma growth, self-renewal, and tumorigenesis	Regulating oncogenes, such as upregulated ADAM19, EPHA3, and KLF4 and tumor suppressors, such as downregulated CDKN2A, BRCA2, and TP53I11	[43]
	Glioblastoma	Oncogene	Reducing the sensitivity to γ-irradiation and reduced DNA repair in vitro and promoting tumor growth in vivo	Enhancing the SOX2 mRNA stability by recruiting of Human antigen R (HuR) on the m6A sites	[24]
	Lung cancer	Oncogene	Promoting growth, survival, and invasion of human lung cancer cells	Promote the protein translation, such as EGFR, TAZ, MAPKAPK2 (MK2), and DNMT3A	[20]
	Lung cancer	Oncogene	Promoting tumor growth in vivo	Enhancing the translation of BRD4 by interacting with eukaryotic translation initiation factor 3 subunit h (eIF3h).	[47]
	Liver cancer	Oncogene	Promoting HCC cell proliferation and migration	Regulating its target, SOCS2	[48]
	Bladder cancer	Oncogene	Promoting malignant transformation of uroepithelial cells and bladder cancer tumorigenesis in vitro and in vivo	Promoting the stability of CPCP1 translation by YTHDF1 preferentially recognizing m6A residues on CPCP1 3′-UTR	[49]
	Bladder cancer	Oncogene	Promoting cell proliferation, invasion, and survival in vitro and tumorigenicity in vivo	Promoting directly the expression of AF4/FMR2 family member 4 (AFF4), two key regulators of NF-κB pathway (IKBKB and RELA) and MYC	[50]
	Ovarian carcinoma	Oncogene	Promoting cell proliferation, focus formation, motility, invasion in vitro and tumor formation in vivo	Enhancing the translation of AXL to promote the EMT process	[51]
	Endometrial cancer	Tumor suppressor	Inhibiting cell proliferation, anchorage-independent growth, colony formation, migration and invasion in vitro and tumor growth and metastases in vivo	Affecting multiple AKT pathway components to stimulate AKT activation, such as PHLPP2 (a negative regulator of AKT activation)	[52]
	Breast cancer	Oncogene	Promoting proliferation and inhibiting apoptosis in vitro	Promoting the expression of HBXIP through m6A modifications and be inhibited by let-7g which could be arrested by HBXIP	[53]
METTL14	Leukemia	Oncogene	Inhibiting differentiation of AML. Promoting self-renewal of leukemia stem/initiation cells	Regulating mRNA stability and translation of MYB and MYC, be inhibited by SPI1	[54]
	Glioblastoma	Oncogene	Promoting glioblastoma growth, self-renewal, and tumorigenesis	Regulating oncogenes, such as upregulated ADAM19, EPHA3, and KLF4 and tumor suppressors, such as downregulated CDKN2A, BRCA2, and TP53I11	[43]
	Endometrial cancer	Tumor suppressor	Inhibiting cell proliferation, anchorage-independent growth, colony formation, migration and invasion in vitro and tumor growth and metastases in vivo	Affecting multiple AKT pathway components to stimulate AKT activation, such as PHLPP2 (a negative regulator of AKT activation)	[52]
	Hepatoma	Tumor suppressor	Inhibiting the migration and invasiveness in vitro and the tumor growth and metastases in vivo	Regulating the miRNA processing by binding to DGCR8	[55]
	Hepatoma	Oncogene	Promoting HCC cell proliferation and migration	Regulating its target, SOCS2	[56]
FTO	Glioblastoma	Tumor suppressor	Suppressing glioblastoma growth, self-renewal, and tumorigenesis	Regulating oncogenes, such as upregulated ADAM19, EPHA3, and KLF4 and tumor suppressors, such as downregulated CDKN2A, BRCA2, and TP53I11	[43]
	Leukemia	Oncogene	Promoting cell transformation and leukemogenesis, inhibiting cell differentiation in AML	Regulating expression of targets such as ASB2 and RARA by reducing m6A levels in these mRNA transcripts	[45]
	Lung cancer	Oncogene	Promoting the tumor progression of lung cancer	Promoting the stability of MZF1 mRNA transcript	[57]
	Cervical squamous cell carcinoma	Oncogene	Promoting the chemo-radiotherapy resistance in vitro and in vivo	Regulating expression of β-catenin by reducing m6A levels and increasing ERCC1 activity	[25]
ALKBH5	Glioblastoma	Oncogene	Promoting proliferation in vitro and GSCs tumorigenesis in vivo	Promoting expression of FOXM1 nascent transcripts by interacting with FOXM1-AS	[44]
	Breast cancer	Oncogene	Promoting capacity for tumor initiation to increase the number of breast cancer stem cells	Strengthening NANOG mRNA stability by catalyzing m6A demethylation in 3′ UTR of NANOG	[21]
YTHDF1	Melanoma and colon cancer	Oncogene	Promoting tumor growth by regulating tumor immune	Promoting the expression of transcripts encoding lysosomal proteases to degradate tumor antigen	[58]
YTHDF2	Liver cancer	Oncogene	Promoting HCC cell proliferation and migration	Interacting with METTL3 to regulate its target, SOCS2	[48]
IGF2BP1	Ovarian and Liver cancer	Oncogene	Promoting tumor cell growth and cell invasion	Enhancing SRF mRNA stability in an m6A-dependent manner	[59]

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